Bioworld Insight

BioWorld Insight The news source of record covering the development of innovative human therapies October 30, 2017 Actionable Intelligence • Incisive Analysis Volume 25, No. 44 Society needs to urgently address antimicrobial resistance By Peter Winter, Editor The challenge of antimicrobial resistance (AMR) is one we need to urgently solve. In the U.S., the CDC estimates at least 2 million people become infected with bacteria that are resistant to currently available antibiotic therapies annually and approximately 23,000 people will die each year as a direct result of those infections. The threat of AMR has certainly been recognized worldwide and has become a top priority for global policy and public health.

See AMR, page 3

Cheaper and faster also testing the drug in combination with immune Oncology drugs checkpoint inhibitors. “You often hear people say inhibiting PD-1 move to China seeking and CCR4 is like reducing the brake on a car. Plinabulin is like adding the fuel,” Huang patients and approvals explained. Nevertheless, she sees opportunities By Brian Orelli, Staff Writer for plinabulin in combination with both With a third of the world’s cancer patients residing chemotherapy and immune checkpoint inhibitors, Inside in China and upward of half of them enrolling in “Chemotherapy isn’t going away; nivolumab only clinical trials, small U.S.-based companies are has a 20 percent response rate.” Money raised by biotech looking across the Pacific to test their oncology On the neutropenia side, last week the company in 2017 drug candidates. enrolled its first patient in China in the global page 4 The advantages of lower cost and increased speed phase II/III trial testing plinabulin as a prevention of chemotherapy-induced neutropenia. The Week in review are clear, according to Lan Huang, CEO of New page 2 York-based Beyondspring Inc. Huang estimated See Oncology, page 4 that Beyondspring’s phase III trial will cost $20 million to $30 million, compared to $100 million Word on the street to $200 million if it ran the same trial in the U.S. Money raised by biotech: 2017 vs. 2016 page 2 exclusively. On the speed side, she estimated a Jan. 1 – Oct. 26, 2017: $38,697M phase III program can be run in two to three years Week in Washington Jan. 1 – Oct. 27, 2016: $27,274M by enrolling patients in both the U.S. and China, page 6 25,000 compared to four to five years for U.S.-based 23,025 trials. Biopharma/nonprofit deals 20,000 page 7 “We’re using plinabulin as a case study to prove this model,” Huang told BioWorld Insight.

14,961 Gainers and losers Beyondspring’s lead asset, plinabulin, binds to 15,000 for the week beta tubulin and activates GEF-H1, a guanine nucleotide exchange factor. The release of GEF-H1 page 14 Millions actives downstream pathways, leading to c-Jun 10,000 activation, release of interleukin cytokines and 8,618 BioWorld stock report 7,054 6,951 the maturation of dendritic cells. page 15 5,464 The process has a two-pronged effect with the 5,000 interleukins, especially interleukin-6, helping to prevent neutropenia – low levels of neutrophils 0 – that is often a side effect of chemotherapy. Public offerings Public/Other* Private biotechs And the dendritic cells help with tumor antigen * Includes financings of public biotech firms with the exceptions of presentation, which encourages the immune public offerings and certain investments from corporate partners. system to attack the tumor, so Beyondspring is

Week in review Word on the street

Financings “We are still in a system where we are delivering Star Wars Ablynx NV generated just over $200 million in an upsized IPO. advancements and technologies into the Flintstones health care system.” ADC Therapeutics SA generated $200 million in a private financing round. Freda Lewis-Hall, chief medical officer at Pfizer Inc., speaking at the Cleveland Clinic’s 15th Medical Innovation Summit Adial Pharmaceuticals Inc. has filed to raise $16 million in its IPO. “Essentially, this means that cell therapy products derived from Allena Pharmaceuticals Inc. has established terms for its IPO one starting cell line (ES cell or iPS cell), edited by ‘Universal by planning to sell 5.33 million shares of its common stock Donor Cell’ technology, can then be applied to any recipients, priced between $14 and $16 per share. which may enhance efficiencies in our regenerative medicines Corbus Pharmaceuticals Holdings Inc. priced a $32.5 million business.” underwritten public offering. Yoshitsugu Shitaka, president of the Astellas Institute for Regenerative Medicine, on gaining the global rights to use set the price for its upcoming IPO at $5 per share. Genprex Inc. Universal Cell’s Donor Cell technology It plans to offer a minimum of 2 million shares and a maximum of 4.5 million shares. “If Puerto Rico’s power grid isn’t restored by the end of the year, Hutchison China Meditech Ltd. said it intends to offer $262 many of the drug and device companies with manufacturing million of American depositary shares. facilities there may need to relocate some of their production.” Idera Pharmaceuticals Inc. priced its underwritten public FDA Commissioner Scott Gottlieb offering, with net proceeds expected to be approximately $46.8 told a House subcommittee last Tuesday million. Ignyta Inc. priced an underwritten public offering for gross “Putting the federal government’s purchasing power to work to proceeds of approximately $160 million. save seniors and the taxpayers money is simply common sense. Immune Design Corp. priced a public offering of 19.5 million The fact that we continue to pay retail rates for wholesale shares at $4.10 each. purchases is . . . ridiculous. It’s long past time we put an end [to] this sweetheart deal for big pharma.” Immune Pharmaceuticals Inc. closed its public offering of Peter Welch (D-Vt.), who along with Sen. Bernie Sanders units for gross proceeds of $18 million. (I-Vt.) and Reps. Elijah Cummings (D-Md.) and Lloyd Doggett Prometic Life Sciences Inc. entered a binding letter of intent (D-Texas), is sponsoring legislation to allow Medicare to directly to secure an $80 million line of credit from Structured Alpha LP. negotiate Part D prescription drug prices

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Our newsroom Business office John Borgman (Director of Commercial Competitive Intelligence), Donald R. Lynn Yoffee (News Director), Jennifer Boggs (Managing Editor), Peter Winter Johnston (Senior Director, Current Awareness) (BioWorld Insight Editor), Marie Powers (News Editor), Anette Breindl (Senior Science Editor), Mari Serebrov (Regulatory Editor), Amanda Lanier (Managing Contact us Editor), Karen Pihl-Carey (Analyst), Ann Duncan (Senior Production Editor), Jennifer Boggs, (770) 880-3631 | John Borgman (831) 462 2510 | Anette Ann Marie Griffith (Production Editor) Breindl, (770) 810-3134 | Michael Fitzhugh, (770) 810-3064 | Donald R. Staff writers: Michael Fitzhugh, Randy Osborne, Shannon Ellis, John Fox, Johnston, 678-641-0970 | Nuala Moran, 44-7778-868-579 | Randy Osborne, Brian Orelli, Nuala Moran, Cormac Sheridan, Alfred Romann, Tamra Sami (770) 810-3139 | Marie Powers, (770) 810-3136 | Mari Serebrov, (770) 810-3141 | Cormac Sheridan, 353-87-6864323 | Peter Winter, (770) 810-3142 | Lynn Yoffee, (770) 361-4789 Monday, October 30, 2017 BioWorld Insight Page 3 of 16

AMR Continued from page 1 “If there are not attractive pull mechanisms A panel at the BIO Investor Forum (BIF) held in San Francisco to justify expensive phase II and III studies, recently discussed the incentives now in place to encourage biopharmaceutical companies to participate in that endeavor, there is a risk that push incentives funding where, up until now, many have been reluctant to get involved. may not be sufficient to secure the full devel- Moderator Gregory Frank, director, Infectious Disease Policy opment and commercialization of new AMR at the Biotechnology Innovation Organization (BIO), set the stage with the grim statistic that according to the Review on products. Antimicrobial Resistance, a report funded by the U.K., if drug- The Biotechnology Innovation Organization resistant pathogens continue to proliferate faster than our development of new medicines to treat them, then by 2050, 10 (CARB) initiative and the U.K. government’s call in 2016 for a million lives will be lost due to AMR-related infections each year concerted global effort to tackle antibiotic resistance. at a combined cost to the global economy of $100 trillion. Panelist Heather Shane, executive director, California That is the challenge facing us and solutions will require a Life Science Institute (CLSI) CARB-X, explained that the global effort in order to control. organization, of which CLSI is a part, is designed to sustain and encourage early stage microbial R&D. The goal is to Positive signs accelerate the preclinical discovery and development of global It is not all doom and gloom, however, because over the past antibacterial innovation, including drugs, vaccines, rapid couple of years major initiatives have been implemented diagnostics and devices. CARB-X aims to invest up to $450 to mobilize and fund researchers and companies that will million over five years in at least 20 new antibacterial products ultimately lead to faster development of new technologies and and progress at least two new products into human trials therapies to treat and prevent AMR infections. during that time. On the international stage, the Davos Declaration on AMR was “In addition to the nondilutive funding we are providing released early last year, which was signed by more than 100 companies, we are helping them through early preclinical and companies, organizations and trade groups. The document early clinical development so they reach a stage that makes formally recognized that the current system was not working them more attractive for investors and potential partners,” well and “traditional R&D approaches have largely failed: explained Shane. companies, private and public funders have invested billions As a partner in the consortium, CLSI is one of three CARB-X of dollars over the last 20 years to discover new antibacterials, accelerators, along with MassBio in Boston and the Wellcome yet no new class of antibiotic for gram-negative infections has Trust reached approval in over 40 years.” CARB-X was launched by the U.S. Department of Health and In the light of that, the document called for governments Human Services (HHS), Biomedical Advanced Research and to commit funding and to support the development and Development Authority (BARDA) and the National Institute of implementation of transformational commercial models that Allergy and Infectious Diseases (NIAID) and is funded by BARDA both enhance conservation of new and existing antibiotics, and the Wellcome Trust. while “improving financial and access-related predictability for One of the less understood aspects of the program is the both industry and health systems.” business support that companies are provided, noted Shane. Drawing from BIO’s policy white paper - “Models to Incentivize Currently, CLSI taps into its extensive advisor network to the Antimicrobial Pipeline” – Frank said that there needs to be give operational and strategic business advisory services both push and pull incentives, which BIO strongly supports. to four companies, one of which is San Diego-based Forge Pull incentives are policies designed to create a viable market Therapeutics Inc., which was one of 11 biotech companies demand and to reward success for developing AMR products. to receive funding from CARB-X. (See BioWorld Today, April 3, “If there are not attractive pull mechanisms to justify expensive 2017.) phase II and III studies, there is a risk that push incentives In fact, Forge received the largest awarded grant of $4.8 million funding may not be sufficient to secure the full development and is in line for future potential milestones of $4 million. and commercialization of new AMR products,” the paper says. Panelist David Puerta, chief operating officer and vice president Push incentives are designed to provide direct support for R&D of discovery at Forge, said the company is developing by sponsors, helping to de-risk their efforts to create an AMR small-molecule inhibitors of LpxC, a zinc metalloproteinase product. Those are of particular value in sustaining innovative found only in gram-negative bacteria and is essential for the efforts. formation of their resistant outer membrane. Early stage microbial R&D For that reason, LpxC is an attractive antibiotic target but, due On the “push incentive” side of the equation, Frank noted the to chemistry limitations, attempts to develop therapeutics have work of CARB-X, which was created in response to the U.S. come up empty. government’s 2015 Combating Antibiotic Resistant Bacteria See AMR, page 5

International Council of Harmonization, Huang noted that the Money raised by biotech: Jan. 1 – Oct. 26, 2017 CFDA is stressing quality of the data it receives. (See BioWorld, June 28, 2017.) While there are a lot of patients in China interested in enrolling Private in clinical trials, Huang noted that there’s still plenty of 22% competition for those patients from big international pharma companies and from Chinese domestic drug companies. Huang said she thinks that running the trial jointly in the U.S. helps Public 60% with recruitment in China because Chinese clinicians know the Other U.S. FDA has signed off on the trial design, adding legitimacy to 18% the clinical trial. Huang also pointed to the language and cultural differences between the U.S. and China that need to be bridged, which she understands well, having received a PhD from UC Berkley and Public: $23,025M being trained at Memorial Sloan Kettering Cancer Center before Public/Other: $7,054M founding Wuxi MTLH Biotechnology Co. Ltd. and clinical CRO Private: $8,618M Paramax International in China before both were acquired. Partnering up Oncology Meanwhile, Celgene Corp. has taken a different approach, Continued from page 1 partnering with Beijing-based Beigene Ltd., to gain access to Beigene’s drug pipeline while passing off responsibilities for combination with immune checkpoint inhibitors is further Celgene’s cancer products in China to Beigene (See BioWorld, behind in a pair of investigator-sponsored trials testing July 7, 2017.) plinabulin in combination with Opdivo (nivolumab, Bristol- Myers Squibb Co.) in patients with non-small-cell lung cancer. Summit, N.J.-based Celgene licensed Beigene’s BGB-A317 for $263 million while also investing about $150 million in Beigene, Likewise, San Diego-based Denovo Biopharma LLC is taking taking a 6 percent stake in the company. For its financial a similar approach running its phase III ENGINE trial testing contribution, Celgene gained rights to the PD-1 inhibitor for DB-102 (enzastaurin) plus the chemotherapy cocktail R-CHOP the treatment of solid tumors in the U.S., Europe, Japan and as the first-line treatment for high-risk patients with diffuse rest of the world outside Asia. The companies also agreed to large B-cell lymphoma (DLBCL) in the U.S. and China. Denovo collaborate on up to eight registrational studies for BGB-A317 in opened a new clinical center in Beijing last year and recently solid tumors. received approval from the CFDA for the ENGINE study. And last week the FDA signed off on the IND for the phase III, paving the Also as part of the complex deal, Celgene handed over its China way for Denovo to start the trial. business, giving Beigene a 10-year exclusivity arrangement on distribution of Celgene’s products approved in China as well DB-102 is a PKC-beta inhibitor originally developed by as commercialization rights to Celgene’s phase II avadomide Indianapolis-based Eli Lilly and Co. While looking through the (CC-122). Beigene also has first right of negotiation for any drug clinical data, including the failed phase III, Denovo discovered Celgene wants to launch in China during the first five years of a biomarker, which it aptly named Denovo Genomic Marker 1 the deal. (DGM1), which was associated with improved overall survival in both the phase II and phase III trials. The ENGINE study is Having only closed the deal in August, CEO Mark Alles told designed to only enroll DGM1-positive DLBCL patients. investors on its third-quarter conference call last week that they’d have to wait until the American Society of Hematology Challenges (ASH) meeting in December to get more details on the clinical To maximize efficiency of its phase III trial, Beyondspring plan for BGB-A317, “I think we’re in a sweet spot now in terms needed to get regulators on both sides of the Pacific to agree to of planning, and we should be in pretty good position by ASH to the same clinical trial protocol so it could be used for approval be more specific about trials and opportunity.” s in the U.S. and China. Fortunately “for cancer, the primary endpoint is black and white,” Huang noted, but there are genetic differences in Asian Is your company featured in this issue? patients that need to be accounted for. To prove that the data from the two counties can be combined, Beyondspring is using Promote it on your website or in your investor kit! a central lab to run tests, including looking at the EGFR status of the tumors. For photocopy rights or reprints, please contact Beyondspring went to the U.S. FDA first because, Huang said, Chris Venezia toll free at (855) 260-5607 or, outside that agency “demands the highest quality in the world,” and the U.S. and Canada, at (646) 522-6243, or by email then it worked with the CFDA for approval of the protocol. at [email protected]. Having recently been accepted as a regulatory member to the

Week in review AMR Continued from page 3 Scpharmaceuticals Inc. has filed to raise up to $100 million in an IPO. Forge is using its chemistry platform, which focuses on binding to the metal ions in the enzyme’s active site, to discover novel Spero Therapeutics Inc. has set terms for its IPO and will sell and stable inhibitors, and those are now being optimized in a 5 million shares of common stock priced between $14 and $16 partnership with Evotec AG, of Hamburg, Germany. per share. During the week of the BIF meeting, Forge announced it VBI Vaccines Inc. priced its underwritten public offering and had expanded its existing strategic alliance with Evotec and expects to receive aggregate gross proceeds of $63.5 million. launched the Blacksmith platform to discover a broader range Ymabs Therapeutics Inc. closed a $50 million private of therapeutics targeting metalloenzymes. placement led by HBM Healthcare Investments. According to Puerta, that platform approach starts with metal- Deals ligand interactions to identify selective metal-binding fragment pharmacophores (MBPs), from a proprietary library of more 1st Biotherapeutics Inc. and Neuraly Inc., a startup from than 500 MBPs. Intelligently selected fragments result in Johns Hopkins School of Medicine, have agreed to co-develop greater and more effective chemical diversity to rapidly identify brain penetrant c-Abl inhibitors for Parkinson’s disease. key interactions between a fragment and the metalloenzyme Astellas Pharma Inc.’s U.S.-based regenerative medicine active site. Using bioinorganic and medicinal chemistry center has agreed to pay Universal Cells Inc. up to $124 million principles, Forge said it transforms those MBP fragments into for global rights to use its Universal Donor Cell technology in a therapeutic leads. new cell therapy for an undisclosed indication. To date, Forge said it has performed more than 50 Boehringer Ingelheim International GmbH entered a metalloenzyme screens with library hit rates of greater than 15 strategic partnership for the longitudinal observational study, percent, providing multiple starting points to build selective TARGET-NASH, with Target Pharmasolutions Inc. inhibitors of metalloenzymes across a variety of therapeutic Catalyst Biosciences Inc. and Mosaic Biosciences Inc. areas. agreed to collaborate on the development of Catalyst’s anti-C3 protease assets to treat dry age-related macular degeneration Everything to gain and other inflammatory retinal disorders. A positive influence in the quest for new antimicrobial Corrona LLC and the National Multiple Sclerosis Society are therapies has been the Generating Antibiotic Incentives Now collaborating on the launch of Corrona Multiple Sclerosis (GAIN) Act offering, among other incentives, the FDA’s qualified Registry to study the comparative safety and effectiveness of infectious disease products (QIDP) designation, which allows approved MS therapies. companies to achieve fast track status, priority review and extended exclusivity for subsequently approved drugs. Eisai Co. Ltd. and Biogen Inc. expanded their existing agreement to jointly develop and commercialize investigational That was acknowledged by panelist Ted Schroeder, president Alzheimer’s disease treatments. and CEO, Zavante Therapeutics Inc., who said his firm is in late- stage development with a licensed 40-year old antibiotic – but and inked a three-year drug discovery Evotec AG Tesaro Inc. Zavante wouldn’t have gotten involved without the existence of collaboration to discover and develop small-molecule the GAIN Act. candidates against an undisclosed immuno-oncology target. The company is hoping to win marketing approval in the U.S. is partnering with securing Macrogenics Inc. Incyte Corp., for intravenous Zolyd (fosfomycin), a broad-spectrum antibiotic $150 million up front for a collaboration and license agreement with particular activity against important multidrug-resistant covering MGA-012, its phase I monoclonal antibody that bacteria. (See BioWorld Today, April 6, 2017.) inhibits PD-1. It has long been available in other countries. Without the submitted a proposal to acquire PDL Biopharma Inc. Neos additional period of exclusivity afforded by GAIN, the significant for $10.25 per share in cash, representing a Therapeutics Inc. financial investment required to bring the product to market in premium of 40 percent to the closing price of Neos shares on the U.S. could not have been made, explained Schroeder. s Oct. 25. Editor’s note: In the second part of this feature, the investments . . . And More being made in antibiotics and the antibiotics product pipeline will be examined. Agenus Inc. will launch a new subsidiary, Agentus Therapeutics Inc., which will focus on cell therapy to develop immune- oncology “living drugs” to treat various types of cancer. Alzheon Inc. said the FDA designated ALZ-801, its BioWorld is on Twitter investigational Alzheimer’s treatment, as a fast track drug. Stay connected—follow us on Twitter! Antares Pharma Inc. said the FDA issued a complete response letter on the new drug application for the company’s Xyosted www.twitter.com/bioworld (testosterone enanthate) injection.

should be submitted by Jan. 23. Week in Washington As part of its commitment under PDUFA VI and its The FDA released two draft guidances to help sponsors implementation of the 21st Century Cures Act, the FDA plan and evaluate the potential for drug-drug interactions is seeking comment on how sponsors can collect patient (DDIs) during drug development. “In Vitro Metabolism- and experience data to inform agency decisions. To help it Transporter-Mediated Drug-Drug Interaction Studies” and draft guidance on the issue, the agency will hold a public “Clinical Drug Interaction Studies – Study Design, Data workshop Dec. 18 and will accept comments through Feb. Analysis and Clinical Implications” will update and replace 16, 2018. The FDA plans to publish a discussion document a 2012 revised draft guidance on drug interaction studies. next month to guide the workshop discussion on proposed To support approval, sponsors should define clinically approaches. In particular, the agency is seeking feedback on relevant DDIs between an investigational drug and other standardized nomenclature and terminologies for patient- drugs as part of the assessment of the investigational drug’s focused drug development, methods to collect meaningful overall benefit/risk profile. Relevant DDIs should be known patient input throughout the drug development process, and at the time of the drug’s approval and communicated in methodological considerations for data collection, reporting, labeling. The new in vitro DDI guidance focuses on in vitro management and analysis of patient input. experimental approaches for evaluating metabolizing The FDA is encouraging sponsors to begin using the most enzyme- and transporter-based drug interaction potential current B3-format annual version of the World Health and extrapolation of the in vitro data to decide on the need Organization Drug Global for the coding of concomitant for clinical DDI studies. The other guidance discusses clinical medications in study data provided to support new drug studies that evaluate the potential for DDIs, which alter a applications, abbreviated new drug applications, biologics drug’s pharmacokinetics by modulating the effects of drug license applications and certain investigational new drug metabolizing enzymes and transporters. Together, the two applications. Use of that version will be mandatory for draft guidances provide a systematic, risk-based approach to trials that start after March 15, 2019, according to a notice assessing DDIs, the FDA said. Comments on both guidances published in last Tuesday’s Federal Register. s

Week in review

DBV Technologies Inc.’s shares plunged on news that its Viaskin peanut allergy therapy failed to reach statistical significance in a pivotal phase III trial in children. Durect Corp.’s Posimir (Saber-bupivacaine) failed a phase III study of the extended-release analgesic. Data from the PERSIST study showed a favorable trend but fell short of statistical significance on the primary endpoint of reducing pain on movement over the first 48 hours after surgery. PTC Therapeutics Inc. said it received a complete response letter for the NDA seeking approval of Translarna (ataluren) for the treatment of nonsense mutation dystrophinopathies from the FDA’s Office of Drug Evaluation I. The EMA has pledged better support for the development of advanced tissue medicinal products (ATMPs) based on cells, genes or tissues, in response to repeated complaints by industry that the regulation is overcomplex and in some cases, inappropriate. A plan published jointly with the European Commission’s health directorate, DG Sante, will “streamline procedures” and “better address” the specific requirements of ATMP developers, the EMA said. VBL Therapeutics Inc. said the EMA designated ofranergene obadenovec (VB-111) as an orphan medicinal product for the treatment of ovarian cancer. Zealand Pharma A/S said the FDA Office of Orphan Products Development granted orphan status to glepaglutide for the treatment of the rare disease short bowel syndrome. s

Collaborations between biopharmaceutical companies and government/nonprofit entities: August 1 - October 25, 2017

Principal Partner Start Deal title Technologies company company date August 23andMe and Milken Institute to conduct study 23andMe Inc. Milken Institute Genomics (primary) 8/2/17 on major depressive and bipolar disorders Baylor College of Medicine and Millipore to Baylor College of Merck Millipore Biological therapeutic 8/8/17 develop vaccines for neglected and emerging Medicine infections Cancer Research to conduct phase I clinical Cancer Research UK Biotecnol Ltd. Humanized antibody (primary); 8/10/17 trial for Biotecnol's Tb535H aganist advanced biological therapeutic; chimeric solid tumors, including lung cancer antibody; multivalent antibody; parenteral formulation unspecified; service laboratory deal Diamyd Medical and Cardiff University to Cardiff University Diamyd Medical Biological therapeutic; intradermal 8/10/17 monitor immune response in lymph node cells AB formulation; protein recombinant after administration of Diamyd Cedars-Sinai to conduct preclinical studies on Cedars-Sinai Context Small molecule therapeutic 8/17/17 Context's Sigma1 compounds for pulmonary Medical Center Therapeutics LLC (primary); oral formulation fibrosis MGHCC to develop novel T-cell therapies Crispr Therapeutics Massachusetts Allogenic stem cell therapy 8/22/17 by using Crispr's CRISPR/Cas9 gene editing General Hospital (primary) against cancer Cancer Center (MGHCC) Grid to use Duke's patents to develop human- Duke University Grid Therapeutics Antibody (primary); biological 8/22/17 derived antibody for cancer LLC therapeutic Synergie Lyon Cancer to conduct clinical Fondation Synergie Context Biomarkers deal (primary); 8/17/17 studies on Context's Sigma1 biomarker for Lyon Cancer Therapeutics LLC diagnostic method prostate cancer Evotec to use Fraunhofer IME's technology Fraunhofer Institut Evotec AG Other technologies (primary); 8/3/17 portfolio on its iPSC-based drug discovery Molekularbiologie genomics research Und Angewandte Oekologie Fred Hutchinson to conduct preclinical studies Fred Hutchinson Context Small-molecule therapeutic 8/17/17 on Context's Sigma1 compounds for prostate Cancer Research Therapeutics LLC (primary); animal model; oral cancer Center formulation Zhejiang Hisun Pharmaceutical and IDRI to Infectious Disease Zhejiang Hisun Antibiotic (primary); natural 8/24/17 develop Lilly's TB Initiative's CPZEN-45 against Research Institute Pharmaceutical product; small molecule tuberculosis (IDRI) Co. Ltd. therapeutic; subcutaneous formulation Beijing Collab Pharm and IMM to develop AF-05 Institute of Materia Beijing Collab Small molecule therapeutic 8/29/17 against anxiety Medica Chinese Pharma Co. Ltd. (primary); capsule formulation; Academy of Medical natural product; oral formulation Sciences & Peking Union Medical College Puretech Health to license Glyph Technology Monash University Puretech Health Small molecule therapeutic 8/29/17 from Monash University to identify novel plc (primary) approaches for dysfunctions of the brain, immune and gastrointestinal systems NCI to conduct cancer research using Edico's National Institutes Edico Genome Genomics (primary) 8/2/17 Dragen Bio-IT platform of Health Corp.

Principal Partner Start Deal title Technologies company company date NCSU and UNC School of Medicine to develop North Carolina UNC School of Allogenic stem cell therapy 8/3/17 stem cell treatment for several lung conditions State University Medicine (primary); adult stem cell therapy; biological therapeutic; infusion; intravenous formulation; lung stem cell therapy AFRRI to initiate the Pluristem's PLX-R18 cell Pluristem Armed Forces Mesenchymal stem cell therapy 8/16/17 therapy studies for acute radiation syndrome Therapeutics Inc. Radiobiology (primary); allogenic stem cell Research Institute therapy; biological therapeutic; (AFRRI) hematopoietic stem cell therapy; intramuscular formulation Sillajen to enter into CRADA with NCI to Sillajen Inc. National Cancer Biological therapeutic; infusion; 8/16/17 evaluate the combination of Pexa-Vec with Institute intratumoral formulation; anti-PDL1 and anti-CTLA4 antibodies against intravenous formulation; virus colorectal cancer recombinant Cleveland to develop Soin's TV-1001sr for Soin Neuroscience Cleveland Clinic Small molecule therapeutic 8/10/17 neuropathic pain worldwide Foundation (primary); oral formulation; sustained-release formulation; tablet formulation Alligator Bioscience and Stanford University to Stanford University Alligator Biomarkers deal (primary) 8/7/17 predict clinical efficacy of pipeline candidates Bioscience AB through the analysis of systemic biomarkers Takeda Pharmaceutical and Stanford Stanford University Takeda Small molecule therapeutic 8/15/17 University to collaborate on novel therapeutic Pharmaceutical (primary) discovery Co. Ltd. Tempus to provide genomic sequencing and Tempus Inc. University of Genomics (primary); service 8/3/17 analytics for University of Virginia's patients in Virginia laboratory deal its LGL Leukemia Registry iPS Academia to use TWMU's cell related Tokyo Women's iPS Academia Stem cell therapy (primary) 8/10/17 patent portfolio Medical College Japan Inc. (TWMU) University of British Columbia to evaluate University of British Lexaria Other technologies (primary); 8/31/17 cardiovascular and cognitive health effects of Columbia Bioscience Corp. capsule formulation; natural Lexaria's TurboCBD product Yale University and X4 Pharmaceuticals to X4 Pharmaceuticals Yale University Animal model (primary); capsule 8/2/17 develop and study a genetic model of WHIM Inc formulation; oral formulation; small syndrome molecule therapeutic September Natera and Aarhus University to use Signatera Aarhus University Natera Inc. Biomarkers deal (primary) 9/20/17 technology to evaluate ctDNA as biomarker in diagnosis and treatment of bladder cancer Biohaven and ADCS to evaluate trigriluzole for Alzheimer's Disease Biohaven Small molecule therapeutic 9/15/17 mild-to-moderate Alzheimer's disease Cooperative Study Pharmaceutical (primary); capsule formulation; oral (ADCS) Holding Co. Ltd. formulation; prodrug Bayer and Vanderbilt University Medical Center Bayer AG Vanderbilt Small molecule therapeutic 9/11/17 to develop two new drug candidates against University (primary) kidney diseases Glythera to develop Cancer Research UK's Cancer Research UK Glythera Ltd. Antibody conjugated (primary); 9/26/17 novel CDK11 inhibitor payload series for antibody drug conjugate; biological development of multiple antibody-drug therapeutic conjugates against cancer worldwide

Principal Partner Start Deal title Technologies company company date CIMA and Alligator to conduct research on Center for Applied Alligator Other technologies (primary) 9/13/17 biology of 4-1BB Medical Research Bioscience AB (CIMA) Dxterity and City of Hope Medical Center to City of Hope Dxterity Genomics (primary); diagnostic 9/21/17 develop a cancer genomic blood test Medical Center Diagnostics method Summit and cTAP to accelerate the Collaborative Summit Small molecule therapeutic 9/25/17 development of drugs for Duchenne muscular Trajectory Analysis Therapeutics plc (primary); nanoparticle formulation dystrophy Project oral; oral formulation; oral liquid formulation University of Texas MD Anderson to Convergene LLC MD Anderson Small molecule therapeutic 9/18/17 characterize Convergene’s CG-223 and CG-250 Cancer Center (primary) in ovarian carcinoma Massachusetts Eye and Ear to evaluate Editas' Editas Medicine Inc. Massachusetts Biological therapeutic; ophthalmic 9/12/17 EDIT-101 for Lebers congential amaurosis Eye & Ear formulation; virus recombinant Infirmary Leap Therapeutics and EORTC to evaluate European Leap Monoclonal antibody humanized 9/8/17 DKN-01 in combination with atezolizumab and Organisation for Therapeutics Inc. (primary); antibody fragment; paclitaxel against cancers in Europe Research and biological therapeutic; Treatment of chimeric monoclonal antibody; Cancer (EORTC) immunoglobulin-G; infusion; intravenous formulation; monoclonal antibody human; protein recombinant Repairon to use iPS Academia's cell derived iPS Academia Repairon GmbH Cell therapy (primary) 9/15/17 tissue products for regenerative therapy of Japan Inc. myocardial damage Morphotek and Johns Hopkins University to Johns Hopkins Morphotek Inc. Monoclonal antibody (primary) 9/6/17 research and develop monoclonal antibody University School of based therapies for cancer Medicine Juntendo University and Heptares Juntendo Heptares Small molecule therapeutic 9/1/17 Therapeutics to develop leukotriene receptor University Therapeutics Ltd. (primary) modulators for intractable skin/intestinal ulcers MD Anderson and Pfizer to evaluate immuno- MD Anderson Pfizer Inc. Drug combination (primary); 9/29/17 oncology combinations for solid tumors and Cancer Center biological therapeutic; immuno- acute myelogenous leukemia oncology; immunoglobulin-G; infusion; intravenous formulation; monoclonal antibody conjugated; monoclonal antibody human; oral formulation; small molecule therapeutic; tablet formulation Indevr to license Influenza Mabs from Icahn Mount Sinai Medical Indevr LLC Monoclonal antibody (primary) 9/19/17 School of Medicine to quantify neuraminidase Center in Vaxarray system worldwide NIAID to conduct phase I trials on Geom's GT-1 National Institute Geom Small molecule therapeutic 9/13/17 for gram-negative bacteria infections of Allergy and Therapeutics Inc. (primary); antibiotic Infectious Diseases Iovance Biotherapeutics and OSUCCC to Ohio State Iovance Cell therapy (primary); biological 9/7/17 develop TIL, MIL and peripheral blood- University Biotherapeutics therapeutic; infusion; parenteral associated lymphocyte technologies in Comprehensive Inc. formulation unspecified; systemic hematologic malignancies Cancer Center formulation unspecified; (OSUCCC) T-lymphocyte

Principal Partner Start Deal title Technologies company company date Nevakar and Princeton University to develop Princeton Nevakar LLC Nanoparticle formulation (primary) 9/29/17 nanoparticle treatments against cancer and University infection Project ALS and Amylyx Pharmaceuticals to Project ALS Amylyx Small molecule therapeutic 9/7/17 conduct research on AMX-0035 against ALS Pharmaceuticals (primary); drug combination; oral Inc. formulation Angle to license Queen Mary University of Queen Mary Angle plc Biomarkers deal (primary) 9/13/17 London's intellectual property related to University of megakaryocytes worldwide London NCATS to enter CRADA with Retrophin to Retrophin Inc. National Center Small molecule therapeutic 9/5/17 identify potential small-molecule therapeutics For Advancing (primary) for NGLY1 deficiency Translational Sciences Casebia and Seattle Childrens to develop Seattle Children's Casebia T-lymphocyte cell therapy 9/27/17 CRISPR/Cas9 gene-edited regulatory T cells for Hospital Therapeutics LLC (primary); biological therapeutic; autoimmune diseases worldwide gene technology; protein engineering Innovent Biologics to develop SIOC's IDO Shanghai Institute Innovent Small molecule therapeutic 9/4/17 small-molecule inhibitor for cancer worldwide of Organic Biologics Inc. (primary) Chemistry Southern Research and UTHSC to conduct Southern Research University of Small molecule therapeutic 9/20/17 research on discovery and development of new Institute Tennessee Health (primary) antimicrobial agents Science Center (UTHSC) Nantes University and Ose to develop anti-C- Universite de Ose Immuno- Antibody (primary); biological 9/28/17 type lectin receptor antibody for cancer with Nantes therapeutics therapeutic worldwide exclusive option to further products TCB and UCL to develop gamma delta T University College TC Biopharm Ltd. Cell therapy (primary); chimeric 9/5/17 cells genetically modified to express an anti- London antigen receptor T cell therapy; CD33 chimeric antigen receptor for acute infusion; intravenous formulation; myelogenous leukemia protein fusion; receptor chimeric; T-lymphocyte University of Bergen to evaluate Moleculin University of Bergen Moleculin Biotech Small molecule therapeutic 9/6/17 Biotech's WP-1122 in combination with Avastin Inc. (primary); oral formulation; against brain cancer Prodrug Novartis and University of California at University of Novartis AG Small molecule therapeutic 9/28/17 Berkeley to discover therapeutics in infectious California at (primary) diseases and cancer areas Berkeley University of Georgia and Epivax to develop a University of Epivax Inc. Biological therapeutic; parenteral 9/18/17 protective avian influenza A (H7N9) vaccine Georgia formulation unspecified Hawaii Biotech to develop University of University of Hawaii Hawaii Biotech Biological therapeutic; protein 9/25/17 Hawaii's thermostable trivalent Ebola virus Inc. recombinant; virus recombinant vaccine Pascal Biosciences to sign option to acquire a University of New Pascal Monoclonal antibody (primary); 9/11/17 therapeutic monoclonal antibody for BCP-ALL Mexico (UNM) Biosciences Inc. biological therapeutic from UNM worldwide Revive Therapeutics to acquire a license of University of South Revive Other technologies (primary); 9/19/17 patent portfolio of cannabinoids from SCRF Carolina (South Therapeutics Ltd. natural product Carolina Research Foundation)

Principal Partner Start Deal title Technologies company company date University of Kentucky to develop Valerion Valerion University of Monoclonal antibody conjugated 9/6/17 Therapeutics' VAL-0417 against lafora disease Therapeutics LLC Kentucky (primary); antibody fragment; biological therapeutic; enzyme; monoclonal antibody murine; parenteral formulation unspecified; protein fusion Xbiotech and Cedars-Sinai Medical Center to Xbiotech Inc. Cedars-Sinai Monoclonal antibody 9/20/17 evaluate MABp-1 in combination with Onivyde Medical Center human (primary); biological and 5-fluorouracil in pancreatic cancer therapeutic; immuno-oncology; immunoglobulin-G; infusion; intravenous formulation; liposome formulation; nanoparticle formulation; nanoparticle formulation injectable; small molecule therapeutic; subcutaneous formulation Sens Research Foundation and Yale University Yale University Sens Foundation Monoclonal antibody (primary) 9/18/17 to develop anti-glucosepane antibodies for Inc. tissue damage October TB Alliance and Astellas Pharma to discover Astellas Pharma The Global Small molecule therapeutic 10/18/17 novel drugs for tuberculosis Inc. Alliance for (primary) TB Drug Development Massachusetts General Hospital to develop Biopharmx Corp. Massachusetts Dermatological gel formulation 10/11/17 Biopharmx's pharmacokinetic tomography to General Hospital (primary); antibiotic; deliver BPX-01 for acne vulgaris dermatological formulation; small molecule therapeutic Harmony to develop and commercialize Bioprojet, Societe Harmony Small molecule therapeutic 10/6/17 Bioprojet's pitolisant for sleep and other Civile de Recherche Biosciences LLC (primary); capsule formulation; oral central nervous system disorders in the U.S. formulation Amgen and BCH to identify genes and drug Boston Children's Amgen Inc. Genomics (primary) 10/16/17 targets for severe pain syndromes Hospital Contravir and Li Ka to explore the mechanisms Contravir Li Ka Shing Small molecule therapeutic 10/17/17 of action of CRV-431 and TXL as a potential Pharmaceuticals Institute of (primary); lipid; oral formulation; treatment against hepatitis B virus infection Inc. Virology oral sustained release formulation; prodrug Dana-Farber/Brigham and Women's Cancer Dana-Farber/ Kite Pharma Inc. Chimeric antigen receptor T cell 10/19/17 Center to conduct study for Kite Pharma's Brigham and therapy (primary); biological Yescarta for non-Hodgkin Lymphoma Women's Cancer therapeutic; immuno-oncology; Center infusion; intravenous formulation; protein fusion; receptor chimeric; T-lymphocyte University of Liverpool to develop Forma's Forma Therapeutics The University of Small molecule therapeutic 10/19/17 USP7 inhibitors against cancer Inc. Liverpool (primary) Fraunhofer ITEM and Griffith University to Griffith University Fraunhofer- Small molecule therapeutic 10/12/17 develop novel anti-infective drugs Institute of (primary) Toxicology and Experimental Medicine Universidad de Sevilla to develop a time- Growblox Sciences Universidad de Sustained release formulation 10/10/17 released version of GB Sciences' chronic pain Inc. Sevilla (primary); nanoparticle formulation formulations

Principal Partner Start Deal title Technologies company company date Institut Curie and IRPF to develop new Institut Curie Pierre-Fabre Immuno-oncology 10/20/17 therapeutic for cancer treatment Research Institute (IRPF) MD Anderson and Navire Pharmaceuticals to MD Anderson Navire Small molecule therapeutic 10/4/17 develop SHP-2 tyrosine phosphatase inhibitors Cancer Center Pharmaceuticals (primary) for cancer AMRC to develop Medivir's metallo-β- Medivir AB Antimicrobial Antibiotic (primary) 10/5/17 lactamase inhibitor program for pneumoniae Resistance Centre worldwide AMRC to develop Medivir's MBLI program for Medivir AB Antimicrobial Antibiotic (primary); antibiotic 10/5/17 escherichia coli and klebsiella pneumoniae Resistance Centre resistance; drug combination worldwide Inspyr and NIAID to evaluate Inspyr's ARM- National Institute Inspyr Small molecule therapeutic 10/23/17 based compounds against graft-vs-host of Allergy and Therapeutics Inc. (primary) disease Infectious Diseases iPS Academia to license Nihon University's Nihon University iPS Academia Pluripotent stem cell therapy 10/10/17 patent covering highly efficient method for Japan Inc. (primary) establishing induced pluripotent stem cells Peter MacCallum Cancer Centre to evaluate Peter MacCallum Aprea Small molecule therapeutic 10/16/17 phase Ib/II clinical study of Aprea Therapeutics' Cancer Centre Therapeutics AB (primary); infusion; intravenous APR-246 in combination with cisplatin and formulation; prodrug 5-fluorouracil for esophageal cancer Hospital of the Transfiguration of Lord to Poznan University Moleculin Biotech Small molecule therapeutic 10/3/17 conduct clinical trial to study Moleculin of Medical Sciences Inc. (primary); antibiotic; infusion; Biotech's Annamycin against acute intravenous formulation; liposome myelogenous leukemia formulation Regeneron and BARDA to discover, develop Regeneron U.S. Health and Antibody (primary); biological 10/2/17 and manufacture a portfolio of antibodies Pharmaceuticals Human Services therapeutic targeting up to 10 pathogens including Inc. Department influenza virus (Biomedical Advanced Research and Development Authority) Cerevance to use Rockefeller's technology to Rockefeller Cerevance Inc. Other technologies (primary); small 10/17/17 profile specific cell populations in human brain University molecule therapeutic tissue to develop new therapeutics against neurological and psychiatric diseases Shangpharma and SRI to develop enzyme Shangpharma SRI International Small molecule therapeutic 10/9/17 inhibitors for neuroinflammation and Innovation (primary) Alzheimer's disease Southern Research and Bionetix to develop Southern Research Bionetix Inc. Small molecule therapeutic 10/2/17 methyl transferase inhibitors for cancer Institute (primary) Neximmune and LLS to advance AIM-ACT into The Leukemia & Neximmune Inc. Antigen presentation system 10/17/17 phase I against high-risk acute myelogenous Lymphoma Society (primary); biological therapeutic; leukemia parenteral formulation unspecified The Lieber Institute and the VA to discover and The Lieber U.S. Department Small molecule therapeutic 10/10/17 identify novel therapeutic targets for PTSD Institute For Brain of Veterans Affairs (primary) Development Zealand Pharma to identify peptide Torrey Pines Zealand Pharma Peptide (primary) 10/4/17 therapeutics using TPIMS' peptide libraries for Institute for A/S gastrointestinal and metabolic diseases Molecular Studies (TPIMS)

Principal Partner Start Deal title Technologies company company date AIRM and Universal Cells to research, develop Universal Cells Inc. Astellas Institute Cell therapy (primary); biological 10/19/17 and commercialize novel cell therapy for for Regenerative therapeutic undisclosed indication using Universal Donor Medicine Cell technology worldwide GB Sciences to use Universidad de Svilla's Universidad de Growblox Oral formulation (primary); 10/17/17 intellectual property related to time-released Sevilla Sciences Inc. nanoparticle formulation cannabinoid formulation for neuropathic pain worldwide Moleculin Biotech and University of Bergen University of Bergen Moleculin Biotech Small molecule therapeutic 10/11/17 to conduct research on brain metastasis Inc. (primary); oral formulation inhibition by WP-1066 Telix to develop University of Melbourne's University of Telix Imaging (primary); antibody 10/18/17 technology for use with cancer targeting Melbourne Pharmaceuticals agents Ltd. Immune Bio to license University of University of Inmune Bio Inc. Small molecule therapeutic 10/9/17 Pittsburgh's intellectual property to target Pittsburgh (primary); immuno-oncology; other myeloid-derived suppressor cells in cancer technologies University of Virginia School of Medicine University of Inspyr Small molecule therapeutic 10/2/17 and Inspyr to conduct a preclinical study Virginia School of Therapeutics Inc. (primary) of adenosine receptor modulator-based Medicine compounds C. difficile infection Bar-Ilan University to develop Urifer's E-260 for Urifer Ltd. Bar-Ilan Small molecule therapeutic 10/17/17 cancer University (primary) Winthrop Hospital to evaluate Inspyr's Winthrop-University Inspyr Small molecule therapeutic 10/4/17 adenosine receptor agonists for Hospital Therapeutics Inc. (primary) atherosclerosis Notes This chart includes only biopharmaceutical deals between companies and government or nonprofit entities. Deals between two companies, as well as mergers and acquisitions, and grants or contract awards are highlighted in separate charts. For more information about individual companies and/or products, see Clarivate Analytics Cortellis.

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10 biggest U.S. gainers for the week 10 biggest U.S. losers for the week

Share price by percent Share price by dollars Share price by percent Share price by dollars

Neos Thera 30.52 Beyondspring 6.81 DBV Technologies -50.66 Biogen -30.36 Beyondspring 23.49 Alnylam Pharma 5.22 Insys -24.57 DBV Technologies -24.35 Medicinova 17.43 Blueprint Medicine 5.07 Uniqure -20.19 Regeneron Pharma -23.76 Aimmune Thera 16.45 Aimmune Thera 4.22 Celgene -19.09 Celgene -23.16 Hutchison China 14.30 Hutchison China 3.97 Coherus Biosci -18.98 Alexion Pharma -10.40 Macrogenics 9.70 Avexis 3.75 Omeros -18.42 Jazz Pharma -10.10 Cellectis 9.41 Neurocrine Biosci 3.11 Mannkind -18.00 Ionis Pharma -7.99 Blueprint Medicine 7.81 Spark Thera 3.10 Celldex Therap -17.12 Amgen -7.68 Adaptimmune 7.27 Cellectis 2.86 The Medicines Co. -16.72 The Medicines Co. -5.68 Dynavax 6.37 Neos Thera 2.35 Collegium Pharma -15.33 Intercept Pharma -5.42

BioWorld stock report for public biotechnology companies

Company Symbol Close Close % Change Vol Company Symbol Close Close % Change Vol 10/20 10/27 Week YTD (000) 10/20 10/27 Week YTD (000)

Abeona Thera ABEO 19 17.3 -8.95 256.70 5676 Cardiome CRME 1.79 1.31 -26.82 -52.54 1174 AC Immune ACIU 11.87 11.65 -1.85 -10.25 166 Casi Pharma CASI 2.37 2.02 -14.77 75.65 3635 Acadia Pharma ACAD 36.32 35.04 -3.52 21.50 5141 Catabasis Pharma CATB 2.31 2.12 -8.23 -41.27 1997 Acceleron Pharma XLRN 36.57 38.12 4.24 49.37 1995 Catalyst Biosciences CBIO 5.03 4.73 -5.96 -51.49 505 Acelrx Pharma ACRX 2 1.85 -7.50 -28.85 5631 Catalyst Pharma CPRX 2.76 2.75 -0.36 161.90 4160 Achaogen AKAO 13.88 13.63 -1.80 4.69 5085 Celgene CELG 121.33 98.17 -19.09 -15.19 117129 Achieve Life Sci ACHV 1.92 2.07 7.81 -62.36 5600 Celldex Therap CLDX 2.92 2.42 -17.12 -31.64 8336 Achillion ACHN 4.15 3.93 -5.30 -4.84 8785 Cellect Biotech APOP 7.82 9.05 15.73 192.88 1842 Aclaris Thera ACRS 26.09 24.69 -5.37 -9.03 836 Cellectis CLLS 30.39 33.25 9.41 96.17 1540 Acorda Therap ACOR 27.2 26.85 -1.29 42.82 2163 Cellular Biomedicine CBMG 9.6 9.6 0.00 -26.72 82 Adamas Pharma ADMS 19.26 19.51 1.30 15.44 4611 Cel-Sci CVM 1.87 1.65 -11.76 -1.79 924 Adamis ADMP 5.35 5.4 0.93 71.43 3474 Celsion CLSN 3.76 2.31 -38.56 -45.65 6789 Adaptimmune ADAP 7.15 7.67 7.27 89.38 1477 Celyad CYAD 62.5 58 -7.20 226.58 30 Adma Biologics ADMA 3.05 2.76 -9.51 -46.09 108 Cempra CEMP 2.8 2.13 -23.93 -23.93 4508 Aduro Biotech ADRO 9.2 8.3 -9.78 -27.19 2251 Cerus CERS 2.99 2.88 -3.68 -33.79 2869 Advanced Acceler AAAP 73.56 72.91 -0.88 172.46 2448 Chemocentryx CCXI 7.03 7 -0.43 -5.41 500 Advaxis ADXS 3.79 3.18 -16.09 -55.59 4906 Chiasma CHMA 2.5 2.2 -12.00 12.82 275 Aeglea Biothera AGLE 5.05 4.38 -13.27 0.69 212 Chimerix CMRX 5.07 4.9 -3.35 6.52 693 Aeolus AOLS 0.08 0.07 -12.50 -63.16 47 Cidara Therap CDTX 7.5 7.7 2.67 -25.96 578 Aerie Pharma AERI 65.1 63.3 -2.76 67.24 2794 Clearside Biomedical CLSD 7.9 7.12 -9.87 -20.36 593 Aeterna Zentaris AEZS 2.03 1.88 -7.39 -47.78 1186 Clementia Pharm CMTA 16.08 16.11 0.19 0.69 151 Aevi Genomic Med GNMX 1.73 1.72 -0.58 -66.80 3919 Cleveland Biolabs CBLI 3.11 3.01 -3.22 111.97 324 Affimed Thera AFMD 2.15 1.98 -7.91 10.00 1053 Clovis Oncology CLVS 77.5 76.99 -0.66 73.32 6859 Affymax AFFY 0.03 0.03 0.00 -52.98 20 Codexis CDXS 7.3 6.6 -9.59 43.48 850 Agenus AGEN 4.33 3.67 -15.24 -10.92 26854 Coherus Biosci CHRS 13.7 11.1 -18.98 -60.57 3313 Agile Thera AGRX 4.99 4.61 -7.62 -19.12 630 Collegium Pharma COLL 11.74 9.94 -15.33 -36.16 2604 Agios Pharma AGIO 67.25 64.43 -4.19 54.40 2190 Compugen CGEN 3.75 3.25 -13.33 -36.27 394 Aileron Thera ALRN 13.58 12.36 -8.98 14.44 66 Conatus Pharma CNAT 5.06 4.81 -4.94 -8.73 1409 Aimmune Thera AIMT 25.66 29.88 16.45 46.11 11996 Concert Pharma CNCE 16.09 16.65 3.48 61.81 1442 Akcea Thera AKCA 18.44 17.05 -7.54 79.85 1360 Contrafect CFRX 1.04 1.04 0.00 -40.57 266 Akebia Thera AKBA 17.88 17.42 -2.57 67.34 1584 Corcept CORT 18.39 18.64 1.36 156.75 6741 Alcobra ADHD 1.59 1.5 -5.66 -28.57 5497 CorMedix CRMD 0.61 0.58 -4.92 -62.09 3382 Alder Biopharma ALDR 11.5 11.2 -2.61 -46.15 5295 Corvus Pharma CRVS 14.78 14.53 -1.69 1.61 116 Aldeyra Thera ALDX 6.75 6.35 -5.93 18.69 1898 Crispr Thera CRSP 19.07 18.95 -0.63 -6.47 986 Alexion Pharma ALXN 139.02 128.62 -7.48 5.12 19010 CTI Biopharma CTIC 3.29 3.16 -3.95 -22.55 598 Alimera Sciences ALIM 1.38 1.25 -9.42 15.74 2013 Curis CRIS 1.57 1.56 -0.64 -49.35 4095 Alkermes ALKS 50.58 49.85 -1.44 -10.31 8718 Cyclacel Pharma CYCC 1.89 1.65 -12.70 -68.81 1687 Alnylam Pharma ALNY 114.7 119.92 4.55 220.30 4932 Cytokinetics CYTK 14.65 14.25 -2.73 17.28 2859 Alpine Immune Sci ALPN 11.03 10.18 -7.71 6.60 191 Cytomx Thera CTMX 20.16 20.28 0.60 84.53 1354 Altimmune Inc ALT 2.66 2.53 -4.89 -92.22 705 Cytrx CYTR 0.36 0.34 -5.56 -8.65 8271 Amag Pharma AMAG 15.6 15.35 -1.60 -55.89 5071 Daré Bioscience DARE 3.09 2.7 -12.62 -55.00 71 Amarin AMRN 3.4 3.33 -2.06 8.12 5221 DBV Technologies DBVT 48.07 23.72 -50.66 -32.48 18492 Amgen AMGN 182.96 175.28 -4.20 19.88 19526 Depomed DEPO 5.39 4.88 -9.46 -72.92 5337 Amicus FOLD 13.59 14.03 3.24 182.29 14972 Dermira DERM 28.61 25.62 -10.45 -15.53 1471 Amphastar Pharma AMPH 18.5 18.41 -0.49 -0.05 870 Dicerna Pharma DRNA 5.51 5.15 -6.53 78.82 326 Ampio Pharma AMPE 1.09 1.07 -1.83 18.86 3411 Dimension Thera DMTX 5.97 6 0.50 37.93 107 Anaptysbio ANAB 64.67 64.72 0.08 280.71 1944 Dova Pharma DOVA 26.73 24.8 -7.22 25.19 321 Ani Pharma ANIP 59.09 57.84 -2.12 -4.59 534 Durect DRRX 0.78 0.78 0.00 -41.79 8106 Anthera Pharma ANTH 1.66 1.72 3.61 -66.86 2384 Dynavax DVAX 20.4 21.7 6.37 449.37 5984 Apollo Endosurgery APEN 4.43 4.15 -6.32 -65.87 175 Edge Thera EDGE 10.46 10.96 4.78 -12.32 246 Apotose Biosci APTO 1.43 1.35 -5.59 -2.88 879 Editas Medicine EDIT 24.01 22.28 -7.21 37.28 4466 Applied Genetic Tech AGTC 4.05 3.8 -6.17 -59.36 407 Egalet EGLT 1.06 1.01 -4.72 -86.80 4072 Apricus Biosciences APRI 1.82 1.67 -8.24 28.46 1044 Eiger Biopharma EIGR 12.8 11.6 -9.38 -0.43 498 Aquinox Pharma AQXP 12.74 11.93 -6.36 -27.74 421 Eleven Biothera EBIO 1.31 1.08 -17.56 -43.46 1557 Aradigm ARDM 4.93 4.28 -13.18 167.50 1099 Emergent Biosol EBS 40.58 40.6 0.05 23.63 1077 Ardelyx ARDX 5.5 5.05 -8.18 -64.44 3151 Emisphere Tech EMIS 0.4 0.37 -7.50 -38.33 33 Arena Pharma ARNA 27.28 27.83 2.02 95.99 1800 Enanta Pharma ENTA 48.16 49.65 3.09 48.21 962 Argenx ARGX 23.31 23 -1.33 44.29 49 Endocyte ECYT 5.19 4.52 -12.91 77.25 5295 Argos Thera ARGS 0.17 0.16 -5.88 -96.73 10539 Enzon Pharma ENZN 0.3 0.3 0.00 -17.81 372 Arqule ARQL 1.11 1.04 -6.31 -17.46 918 Epizyme EPZM 17.05 16.65 -2.35 37.60 2091 Array Biopharma ARRY 11.08 10.91 -1.53 24.12 16740 Esperion Thera ESPR 47.19 47.27 0.17 277.56 3161 Arrowhead Research ARWR 3.87 3.65 -5.68 135.48 2871 Evoke Pharma EVOK 3.44 2.94 -14.53 45.54 7140 Ascendis Pharma ASND 35.07 31.98 -8.81 58.00 729 Exelixis EXEL 27.17 26.63 -1.99 78.60 14709 Assembly Bio ASMB 31.24 31.03 -0.67 155.39 314 Eyegate Pharma EYEG 1.09 1.09 0.00 -33.13 525 Atara Biothera ATRA 14.6 13.6 -6.85 -4.23 839 Fate Thera FATE 4.18 4.54 8.61 80.88 1479 Athenex ATNX 17.13 16.91 -1.28 34.63 433 Fibrogen FGEN 54.65 55.9 2.29 161.21 2160 Atyr Pharma LIFE 5.1 5.2 1.96 141.86 288 Five Prime Thera FPRX 46.8 45.94 -1.84 -8.32 1331 Audentes Thera BOLD 24.98 25.71 2.92 40.72 727 Flex Pharma FLKS 3.39 2.8 -17.40 -46.97 279 Auris Medical EARS 0.79 0.79 0.00 -26.17 1481 Flexion Thera FLXN 23.15 21.63 -6.57 13.72 13693 Avadel Pharma AVDL 10.23 9.45 -7.62 -9.05 625 Foamix Pharma FOMX 6.82 6.04 -11.44 -45.59 477 AVAX Technologies AVXT 0.0016 0.0016 0.00 -63.64 200 Fortress Bio FBIO 3.98 3.8 -4.52 40.74 521 Avenue Thera ATXI 4.71 4.64 -1.49 -43.76 157 Forward Pharma FWP 6.12 5.86 -4.25 115.44 153 Aveo Pharma AVEO 3.18 2.98 -6.29 451.85 11804 G1 Thera GTHX 22.05 21.86 -0.86 45.73 241 Avexis AVXS 100.06 103.81 3.75 117.49 1892 Galena Biopharma GALE 0.39 0.33 -15.38 -82.99 2136 Aviragen Thera AVIR 0.77 0.83 7.79 -32.52 1480 Galmed Pharma GLMD 7.52 8.27 9.97 135.61 187 Axovant Sciences AXON 5.68 5.13 -9.68 -58.70 7524 Gemphire Thera GEMP 9.32 10.22 9.66 30.36 256 Axsome Thera AXSM 5 5 0.00 -25.93 460 Generex Biotech GNBT 2.62 2.75 4.96 -31.08 7 Azurrx BioPharma AZRX 3.51 3.27 -6.84 -31.01 136 Genocea Biosci GNCA 1.46 1.18 -19.18 -71.36 2998 Beigene BGNE 84.03 82.35 -2.00 171.25 1472 Geron GERN 2.05 2.06 0.49 -0.48 5513 Bellerophon Thera BLPH 1.45 1.37 -5.52 163.36 1325 Gilead Sciences GILD 81.21 77.07 -5.10 7.62 58721 Bellicum Pharma BLCM 10.39 9.74 -6.26 -28.49 1811 Global Blood Thera GBT 32.55 34.35 5.53 137.72 6170 Bellus Health BLUSF 0.35 0.34 -2.86 65.85 146 Globeimmune GBIM 0.79 0.8 1.27 175.86 9 Benitec Biopharma BNTC 2.5 2.65 6.00 73.20 255 Glycomimetics GLYC 10.52 10.86 3.23 78.03 2973 Beyondspring BYSI 28.99 35.8 23.49 84.63 16 Gtx GTXI 7.93 8 0.88 51.52 68 Bio Blast Pharma ORPN 2.17 2.39 10.14 129.81 334 GW Pharma GWPH 107.63 102.91 -4.39 -7.91 1302 Biocryst Pharma BCRX 4.8 4.42 -7.92 -30.17 6311 Halozyme HALO 17.82 17.19 -3.54 73.99 5436 Biodelivery Sci BDSI 2.95 2.95 0.00 68.57 1385 Harvard Bio HBIO 3.7 3.25 -12.16 6.56 360 Biogen BIIB 338.1 307.74 -8.98 8.52 13183 Heat Biologics HTBX 0.65 0.56 -13.85 -34.50 873 Biohaven Pharma BHVN 31.67 32.08 1.29 83.31 774 Histogenics HSGX 2.25 2.13 -5.33 27.54 290 Biolinerx BLRX 1.14 1.06 -7.02 15.22 1176 Horizon Pharma HZNP 14.09 13.78 -2.20 -14.83 7333 Biomarin Pharma BMRN 87.75 83.15 -5.24 0.37 8986 Humanigen HGEN 0.42 0.67 59.52 -67.16 225 Biondvax Pharma BVXV 7.62 7.22 -5.25 115.52 32 Hutchison China HCM 27.77 31.74 14.30 133.90 1081 Bio-path Holdings BPTH 0.45 0.41 -8.89 -69.63 1984 Idera Pharma IDRA 2.36 1.56 -33.90 4.00 32573 Biopharmx BPMX 0.24 0.21 -12.50 -45.40 7222 Ignyta RXDX 15.8 15.5 -1.90 192.45 7093 Bluebird Bio BLUE 142.55 140.8 -1.23 128.20 3592 Immune Design IMDZ 5.2 4.1 -21.15 -25.45 14060 Blueprint Medicine BPMC 64.93 70 7.81 149.55 1856 Immune Pharma IMNP 0.94 0.81 -13.83 -77.75 3561 Calithera Biosci CALA 16.45 16.4 -0.30 404.62 1840 Immunocellular IMUC 0.4 0.38 -5.00 -81.46 14323 Cara Thera CARA 12.43 12.71 2.25 36.81 4822 Immunogen IMGN 5.86 5.69 -2.90 178.92 17686

Company Symbol Close Close % Change Vol Company Symbol Close Close % Change Vol 10/20 10/27 Week YTD (000) 10/20 10/27 Week YTD (000)

Immunomedics IMMU 11 11.69 6.27 218.53 10241 Regenxbio RGNX 32.75 28.65 -12.52 54.45 1854 Immuron IMRN 5.25 5.06 -3.62 -51.72 31 Regulus Thera RGLS 1.21 1.05 -13.22 -53.33 2215 Incyte INCY 114.19 116.27 1.82 15.96 9000 Repligen RGEN 37.92 38.12 0.53 23.69 1524 Infinity Pharma INFI 2.28 2.26 -0.88 67.41 6012 Repros RPRX 0.56 0.53 -5.36 -59.85 3582 Innoviva INVA 13.83 11.8 -14.68 10.28 9672 Retrophin RTRX 24.31 24.41 0.41 28.95 962 Inotek Pharma ITEK 2.38 2.53 6.30 -58.52 2533 Revance Thera RVNC 25.5 26.15 2.55 26.33 464 Inovio Pharma INO 6.23 5.83 -6.42 -15.99 6120 Rexahn Pharma RNN 1.85 1.92 3.78 35.21 3709 Insmed INSM 27.55 27.4 -0.54 107.11 2065 Rigel Pharma RIGL 3.89 3.82 -1.80 60.50 6002 Insys INSY 7.61 5.74 -24.57 -37.61 5503 Ritter Pharma RTTR 0.37 0.37 0.00 -86.35 12480 Intec Pharma NTEC 8 8.2 2.50 43.86 155 Rockwell Medical RMTI 7.09 6.03 -14.95 -7.94 1781 Intellia Therapeutics NTLA 28.22 27.58 -2.27 110.37 1496 Rxi Pharma RXII 0.6 0.56 -6.67 -21.65 1220 Intercept Pharma ICPT 66.85 61.43 -8.11 -43.46 4721 Sage Thera SAGE 63.5 64.19 1.09 25.71 2000 Ionis Pharma IONS 64.39 56.4 -12.41 17.92 11792 Sangamo Biosci SGMO 13.45 12.4 -7.81 306.56 7266 Ironwood Pharma IRWD 15.02 15.11 0.60 -1.18 6130 Sarepta Thera SRPT 51.94 47.79 -7.99 74.23 13123 Jazz Pharma JAZZ 144.05 133.95 -7.01 22.86 2223 Savara SVRA 8.49 8.6 1.30 41.45 1275 Jounce Thera JNCE 14.78 13.94 -5.68 -19.19 817 Scynexis SCYX 1.88 1.9 1.06 -40.44 1030 Juniper Pharma JNP 4.55 4.8 5.49 -14.29 378 Seattle Genetics SGEN 63.86 62.73 -1.77 18.87 5635 Juno Thera JUNO 43.71 45.72 4.60 142.55 8238 Selecta Biosci SELB 21.31 20.98 -1.55 22.33 402 Kala Pharma KALA 16.87 15.2 -9.90 -17.79 1136 Seres Thera MCRB 9.98 9.75 -2.30 -1.52 1505 Kalvista Pharma KALV 11.26 12.6 11.90 78.22 2889 Shire SHPG 145.25 142.17 -2.12 -16.56 6527 Kamada KMDA 5 5.15 3.00 -5.50 310 Sienna Biopharma SNNA 20.33 18.22 -10.38 -5.35 169 Karyopharm Thera KPTI 10.97 10.16 -7.38 8.09 740 Sierra Oncology SRRA 1.64 2.15 31.10 46.26 7500 Kempharm KMPH 3.85 3.7 -3.90 25.42 174 Sinovac Biotech SVA 7.02 7.03 0.14 19.15 567 Keryx Biopharma KERX 6.5 5.99 -7.85 2.22 13327 Soligenix SNGX 2.09 2.04 -2.39 -9.33 1315 Krystal Biotech KRYS 9.99 10.04 0.50 -5.64 177 Sophiris Bio SPHS 2.33 2.19 -6.01 -21.79 698 La Jolla Pharma LJPC 34.83 34.3 -1.52 95.66 1333 Sorrento Thera SRNE 2.8 2.47 -11.79 -49.59 4206 Leap Therapeutics LPTX 5.69 5.47 -3.87 -30.41 129 Spark Thera ONCE 81.87 84.97 3.79 70.28 2580 Lexicon LXRX 11.16 10.2 -8.60 -26.25 4417 Spectrum Pharma SPPI 19.37 19.42 0.26 338.37 7752 Ligand Pharma LGND 143.93 144.83 0.63 42.54 908 Spring Bank SBPH 16.57 15.88 -4.16 98.75 197 Loxo Oncology LOXO 86.62 86.5 -0.14 169.34 1785 Stemline Thera STML 11.1 10.8 -2.70 0.93 962 Macrogenics MGNX 17.73 19.45 9.70 -4.84 4974 Strongbridge Bio SBBP 6.15 6.03 -1.95 151.25 632 Madrigal Pharma MDGL 45.01 45.95 2.09 208.39 253 Sucampo Pharma SCMP 10.3 9.68 -6.02 -28.56 1881 Mannkind MNKD 4.11 3.37 -18.00 5.31 41089 Summit Thera SMMT 11.64 10.2 -12.37 19.16 240 Marina Biotech MRNA 2.4 2.01 -16.25 -31.40 20 Sunesis SNSS 1.97 2.11 7.11 -41.71 1072 Marinus Pharma MRNS 5.3 5.99 13.02 493.07 4998 Supernus Pharma SUPN 41.85 41.25 -1.43 63.37 1633 Mateon Thera MATN 0.28 0.28 0.00 -26.80 61 Syndax Pharma SNDX 11.9 10.97 -7.82 53.00 463 Medicinova MNOV 6.14 7.21 17.43 19.57 2832 Synergy Pharma SGYP 2.81 2.7 -3.91 -55.67 30078 MEI Pharma MEIP 2.68 2.59 -3.36 79.86 1209 Synlogic SYBX 15.7 14.75 -6.05 17.06 150 Merrimack Pharma MACK 12.75 11.43 -10.35 -58.83 996 Syros Pharma SYRS 16.51 15.41 -6.66 26.73 794 Mersana Thera MRSN 17.46 14.95 -14.38 6.79 144 Taxus Cardium CRXM 0.14 0.12 -14.29 -21.26 109 Merus MRUS 17.48 16.12 -7.78 -23.64 108 Tenax Thera TENX 0.46 0.46 0.00 -76.41 3214 Microbot Medical MBOT 1.19 1.09 -8.40 -82.13 3627 Tesaro TSRO 116.4 115.62 -0.67 -14.02 2969 Minerva Neurosci NERV 7.45 6.5 -12.75 -44.68 635 Tetralogic Pharma TLOG 0.04 0.05 25.00 -18.43 138 Molecular Templates MTEM 8.93 8.24 -7.73 70.25 651 Tetraphase Pharma TTPH 6.47 5.83 -9.89 44.67 2551 Moleculin Biotech MBRX 2.2 1.8 -18.18 -21.05 2565 TG Therapeutics TGTX 8.6 8.15 -5.23 75.27 7670 Momenta Pharma MNTA 14.05 14.5 3.20 -3.65 3172 The Medicines Co. MDCO 33.98 28.3 -16.72 -16.62 9312 Myokardia MYOK 36.95 37.8 2.30 191.89 1441 Therapix Biosciences TRPX 5.57 5.48 -1.62 36.66 127 Myrexis MYRX 0.04 0.04 0.00 -16.32 31 Titan Pharma TTNP 1.9 2.2 15.79 -45.00 3171 Nabriva Thera NBRV 6.33 5.44 -14.06 -8.72 1878 Tocagen TOCA 9.99 10.34 3.50 -16.95 2766 Nantkwest NK 4.59 4.68 1.96 -18.18 584 Trevena TRVN 1.76 1.54 -12.50 -73.81 4349 Nektar Therap NKTR 24.16 23.61 -2.28 92.42 5886 Trinity Biotech TRIB 5.11 4.75 -7.05 -31.36 423 Neos Thera NEOS 7.7 10.05 30.52 71.79 9775 Ultragenyx RARE 51.51 46.52 -9.69 -33.84 2313 Neothetics NEOT 1.24 1.22 -1.61 8.93 18154 Uniqure QURE 19.27 15.38 -20.19 174.64 12671 Neuralstem CUR 1.42 1.25 -11.97 -64.39 1842 United Therap UTHR 121.01 120.05 -0.79 -16.30 3108 Neurocrine Biosci NBIX 59.03 62.14 5.27 60.57 4137 Urogen Pharma URGN 27.28 28.42 4.18 103.29 213 Newlink Genetics NLNK 10.08 9.52 -5.56 -7.39 6228 Vanda Pharma VNDA 16 14.7 -8.13 -7.84 3372 Northwest Bio NWBO 0.17 0.17 0.00 -50.77 7342 Vascular Biogenics VBLT 6 6.05 0.83 24.74 1878 Novabay NBY 4.3 4.6 6.98 39.39 74 Verastem VSTM 3.95 3.76 -4.81 235.71 2215 Novan NOVN 5.45 6.1 11.93 -77.42 318 Verona Pharma VRNA 14.5 13.48 -7.03 -0.15 29 Novavax NVAX 1.05 1.05 0.00 -16.67 13607 Versartis VSAR 2.65 1.9 -28.30 -87.25 9415 Novelion Thera NVLN 6.55 5.08 -22.44 -39.67 781 Vertex Pharma VRTX 154.63 150.11 -2.92 103.76 12241 Novus Thera NVUS 4.47 3.98 -10.96 -54.77 49 Vical VICL 2.38 2.18 -8.40 -5.22 967 Nymox Pharma NYMX 3.87 3.69 -4.65 38.20 462 Viking Thera VKTX 3 2.41 -19.67 102.52 4881 Obseva OBSV 10.65 10.71 0.56 -8.07 55 Vital Therapies VTL 5.75 5.35 -6.96 22.99 1028 Ocera Thera OCRX 1.09 1.03 -5.50 -50.95 633 Vivus VVUS 0.8 0.7 -12.50 -39.13 4365 Ocular Thera OCUL 5.56 5.77 3.78 -31.06 2377 Voyager Thera VYGR 23.1 22.57 -2.29 77.16 1367 Ohr Pharma OHRP 0.63 0.65 3.17 -56.67 1162 VTV Thera VTVT 7.41 6.61 -10.80 36.85 147 Omeros OMER 18.95 15.46 -18.42 55.85 7798 Wave Life Sciences WVE 22.85 22.45 -1.75 -14.15 680 Oncobiologics ONS 1.35 1.32 -2.22 -56.15 166 Windtree Thera WINT 0.19 0.2 5.26 -84.00 304 Oncomed Pharma OMED 3.76 3.76 0.00 -51.23 596 Xbiotech XBIT 4.12 4.31 4.61 -57.41 390 Onconova Thera ONTX 2.45 2.25 -8.16 -0.88 363 Xencor XNCR 21.29 20.04 -5.87 -23.86 964 Ophthotech OPHT 2.41 2.31 -4.15 -52.17 2117 Xenon Pharma XENE 3.25 2.9 -10.77 -62.34 200 Opko Health OPK 6.96 6.81 -2.16 -26.77 16710 Xoma XOMA 22.65 23 1.55 445.02 450 Orexigen OREX 1.78 1.7 -4.49 -2.30 688 Yield10 Bioscience YTEN 3.45 2.98 -13.62 -14.86 64 Osiris Thera OSIR 4.5 4.75 5.56 -3.26 97 Zafgen ZFGN 3.69 3.5 -5.15 10.06 500 Otonomy OTIC 3.45 2.95 -14.49 -81.45 4323 Zealand Pharma ZEAL 18.43 18.57 0.76 26.93 24 Ovid Thera OVID 7.4 6.58 -11.08 -46.29 541 Ziopharm Oncology ZIOP 5.4 4.77 -11.67 -10.84 11338 Pacira Pharma PCRX 33.5 33.2 -0.90 2.79 4584 Zogenix ZGNX 39.75 38.55 -3.02 217.28 3479 Pain Therapeutics PTIE 3.85 3.87 0.52 -3.01 20708 Zosano Pharma ZSAN 0.85 0.71 -16.47 -8.97 3747 Palatin Tech PTN 0.82 0.74 -9.76 46.51 5545 Zymeworks ZYME 9 8.31 -7.67 -36.08 21 Paratek Pharma PRTK 23.2 21.7 -6.47 40.91 1686 Peregrine Pharma PPHM 4.08 4.56 11.76 111.11 1519 Zynerba Pharma ZYNE 9.73 9.8 0.72 -37.14 2020 Pfenex PFNX 2.75 2.81 2.18 -69.02 435 Pharmos PARS 0.02 0.01 -50.00 -18.03 2 Notes Phaserx PZRX 1.04 0.63 -39.42 -59.35 1411 PLx Pharma PLXP 8.7 7.55 -13.22 -41.02 106 Trading volumes for Nasdaq, Amex and NYSE are recorded as the total number Portola Pharma PTLA 50.65 49.31 -2.65 119.74 3520 Progenics Pharma PGNX 6.41 6.2 -3.28 -28.24 5278 of shares traded (in thousands) on a weekly basis (cumulative Monday through Proqr Thera PRQR 4.4 3.9 -11.36 -20.41 616 Friday); the weekly and YTD % changes are from IPO completion, where Protagonist Thera PTGX 15.93 15.37 -3.52 -30.10 478 Protalix Biothera PLX 0.79 0.71 -10.13 59.55 6402 applicable. Proteon Thera PRTO 2.25 2 -11.11 5.26 114 Average percent change week: -4.19% Proteostasis Thera PTI 2.24 1.98 -11.61 -83.85 601 PTC Thera PTCT 17.79 17.57 -1.24 61.04 11434 Range: -50.66% to +59.52%; Number of companies: 378 Pulmatrix PULM 1.9 1.74 -8.42 194.92 1799 Puma Biotech PBYI 124.65 125.25 0.48 307.98 2403 (not market weighted) Ra Pharma RARX 15.24 13.21 -13.32 -10.01 996 Average percent change year-to-date: +25.51% Radius Health RDUS 35.64 32.5 -8.81 -14.54 6524 Reata Pharma RETA 32.8 30.28 -7.68 38.71 373 Range: -96.73% to +493.07%; Number of companies: 378 Recro Pharma REPH 8.97 8.66 -3.46 7.44 294 (not market weighted) Regeneron Pharma REGN 432.98 409.22 -5.49 11.48 4423