April 2013

NIDDK STUDY SHOWS BI G IMPROVEMENT IN INSIDE THIS ISSUE: DIABETES CONTROL OVER PAST DECADES More people are meeting lyzed data from the Na- 2010. Glucose control was NIDDK DIABETES 1 recommended goals in the tional Health and Nutrition worse in Mexican-Americans CONTROL STUDY three key markers of dia- Examination Surveys from and in younger adults. Only betes control, according to 1988-1994 and 1999- 44 percent of Mexican- N E W T E C H N O L- 2 OGY AVAILABLE a study conducted and 2010. Americans met A1C goals, F R O M N I H funded by the NIH and versus 53 percent of whites

FDA ADVISORY 2 CDC. “The most impressive find- and blacks in 2007-2010 COMMITTEES ing was the significant im- data. People between 20-49 The report shows that, provement in diabetes years old were less likely to NCATS UPDATES 3 from 1988 to 2010, the management over time meet A1C goals than older number of people with dia- across all groups,” said people. NIH FUNDING 3 ANNOUNCEMENTS betes able to meet or ex- Catherine Cowie, Ph.D., ceed all three of the meas- the study’s senior author Goals for A1C, blood pres- P A T I E N T 3 ORGANIZATIONS ures that demonstrate and director of the Diabe- sure, and cholesterol must good diabetes manage- tes Epidemiology Program be individualized for people PAHPA 4 ment rose from about 2 at the NIDDK. with diabetes, as effects of percent to about 19 per- diabetes can differ depend- F I N A N C I A L 4 cent. Each measure also “However, we see a lot of ing on a person’s age, type SERVICES BILL showed substantial im- room for improvement, for of diabetes, diabetes medi- R&D TAX CREDIT 4 provement, with over half everyone, but particularly cations, complications from EXTENDED of people meeting each for younger people and diabetes, and other factors.

SBIR FINAL RULE 5 individual goal in 2010. some minority groups.” For more information on C O M M E N T 5 The measures are A1C — According to 2007-2010 this article, please click LETTERS AND which assesses blood data on Americans with here. LEGISLATION sugar over the previous diabetes: BIO MEETING 6 three months — blood  53 percent met A1C A N N O U N C E M E N T S pressure and cholesterol. goals, compared to 43 When these measures fall percent in 1988-1994 “The report shows SPECIAL POINTS outside healthy ranges, data that, from 1988 to OF INTEREST: people are more likely to  51 percent met blood 2010, the number be burdened by complica- pressure goals, com- of people with  Updates from The tions of diabetes, including pared to 33 percent in diabetes able to National Center for heart disease, stroke, kid- 1988-1994 data meet or exceed all Advancing Transla- ney disease, blindness,  56 percent met choles- three for the tional Sciences measures that and amputation. terol goals, compared (NCATS) (p. 2) demonstrate good to 10 percent in 1988- diabetes Despite improvement, the 1994 data  PAHPA management rose results show continued Reauthorization from about 2 need for better diabetes Improved cholesterol con- (p. 4) percent to about 19 control. In particular, trol was likely due to the percent.” young people and some increase in the use of stat-  Effects of Seques- minority groups were be- tration and Con- ins, a type of cholesterol- low average in meeting the lowering drug, from about tinuing Resolution goals. Legislation (p. 6) 4 percent of people with To gauge diabetes man- diabetes during 1988-1994 agement, researchers ana- to 51 percent during 2007- Focus on Nephrology, Endocrinology, Page 2 Metabolism, & Gastroenterology

NEW TECHNOLOGIES AVA ILABLE FOR LICENSING FROM THE NIH TECHNOLOGY TRANSFER OFFICE

Monoclonal Antibodies (MAbs) Define Human Cytochrome P450 Drug Metablism The application of the invention reported herein will be useful for reducing the incidence of adverse drug reac- tions (ADR) causing serious toxicity and mortality from certain drugs and toxicity from drug-drug interactions (DDI). The MAb system will be useful in the search for new drugs in Drug Discovery. The system engages the use of specific inhibitory monoclonal antibodies (MAbs) to identify, measure and quantitate the role of each hu- man Cytochrome P450 in the metabolism of drugs, NCEs (new chemical entities) or xenobiotics that can be toxic to the human population. Hybridoma clones have been isolated that produce MAbs uniquely specific to human P450s 1A1, 1A2, 2A6, 2C8, 2C9, 2C9*2, 2C19, 2C family (8,9,18,19), 2D6, 2E1, and 3A4/5. The MAbs are highly inhibitory (80-90%) to the enzyme activity of the target P450 and thus the amount of inhibition of the metabolism of the substrate drug incubated with human liver microsomes defines the maximum contribution of the target P450 to the metabolism of the drug or other substrate. The MAbs also immunoblot the target P450 permitting the identification of the target P450 in cells and tissues. In stark contrast to other complex commonly used analytic systems that are selective, the MAb system is specific to the target P450 and is the basis for an extraordinary simple in vitro methodology. The microsome-MAb system (in vitro) defines the contribution of the target P450 to the metabolism of the substrate and identifies substrates metabolized by a single or multiple P450s and P450s catalyzing alternate metabolic pathways. Substrates metabolized by a single P450 or through a specific metabolic route can be used as a marker probe (in vivo) for examining the role of different P450 iso- forms in the metabolism of drugs. They are also used for individual phenotyping for studying the genetic poten- tial for individual drug metabolism. Additional applications include the study of polymorphic P450s to identify the metabolic consequences of the absence of a polymorphic P450 in an individual. The MAbs, listed below, are pre- sent in ascites fluid and are generally useful for all of the procedures described above. Some are also available in purified form.

Java Applet for Modeling Human Metabolism and Energy Expenditure for Adaptive Dieting and Exer- cise Regimens Known methods for predicting weight loss fail to account for slowing of metabolism as weight is lost and there- fore overestimate the degree of weight loss. While this limitation of the 3500 Calorie per pound rule has been known for some time, it was not clear how to dynamically account for the metabolic slowing. The invention pro- vides a Java applet for modeling of human metabolism to improve the weight change predictions. The model has been validated using previously published human data and the model equations have been published. A web- based implementation of the published dynamic model has been created to allow users to perform simulations for planning weight loss interventions in adults and accounts for individual differences in metabolism and body composition.

To learn more about these technologies and to find others available for licensing, please click here.

FDA ENDOCRINOLOGIC A ND METABOLIC DRUGS ADVISORY COMMITTEE

On January 10, the Endocrinologic and Metabolic Drugs The committee members expressed concern about us- Advisory Committee met to discuss the new drug appli- age in these patients, owing to a decreased efficacy, cation (NDA) 204042, canagliflozin tablets, proposed especially when combined with an increased incidence trade name INVOKANA, submitted by Janssen Research of side effects. The committee members further dis- and Development, LLC. Canagliflozin is a member of cussed a discomfort with the relatively small volume of the sodium-glucose co-transporter 2 (SGLT2) inhibi- data to support use in this population. Some commit- tors, and was developed as an adjunct to diet and ex- tee members did suggest a need for separate consid- ercise to improve glycemic control in adults with type 2 eration of renal function in the elderly, as exclusion diabetes mellitus. based only on eGFR could eliminate patients who may actually be suitable candidates for treatment with The committee members generally agreed that the canagliflozin. benefit-risk profile of canagliflozin in patients with type 2 diabetes and moderate renal impairment should be For more information on this meeting, including a full considered differently from the general population. transcript and materials, please click here .

A p r i l 2 0 1 3 Page 3

UPDATES FROM THE NAT IONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES (NCATS)

On December 11, 2012, NCATS partnered with stakeholders in the regulatory, academic, nonprofit, and private sectors to prioritize policy goals and issues and gain perspective on how policy research and analysis can inform translational research. The purpose of the meeting was to gather thought leaders who could provide advice to NCATS leadership on proactively integrating a policy research and analysis agenda in the Center’s mission. By expanding knowledge of relevant policy issues, NCATS leadership hope to build an agenda that can more pro- ductively impact the development of cures and treatments.

Discussion sessions focused on informing regulatory science, navigating intellectual property challenges, stream- lining clinical research, and forming effective strategic alliances. For more information on this meeting, please click here.

On January 23, 2013, NCATS Director Chris Austin, M.D., led his first joint meeting of the NCATS Advisory Coun- cil and Cures Acceleration Network (CAN) Review Board. In his director’s report, Austin commented on NCATS initiatives, programs, and policies. He summarized the Center’s accomplishments over the last three months, shared budget and staff updates, and emphasized research advances.

For more information or a complete videocast of the meeting, please click here.

NIDDK FUNDING ANNOUN CEMENTS

PAR-13-066 Ancillary Studies to the NIDDK Intestinal Stem Cell Consortium (R01) – January 8, 2016

PAR-13-047 Bioengineering Interdisciplinary Training for Diabetes Research (T32) – November 27, 2013

RFA-DK-12-511 Limited Competition for Clinical Trials in Type 1 Diabetes (UC4) – April 4, 2013

PAR-13-028 Research Using Subjects From Selected Type 1 Diabetes Clinical Studies (DP3) – April 3, 2013

PAR-13-007 Early-Stage Pharmacological Validation of Novel Targets and Accompanying Pre-Therapeutic Leads for Diseases of Interest to the NIDDK (R01) – March 8, 2016

PAR-12-265 Ancillary Studies to Major Ongoing Clinical Research Studies to Advance Areas of Scientific Interest within the Mission of the NIDDK (R01) – September 8, 2015

PAR-12-260 Lymphatics in Health and Disease in the Digestive, Cardiovascular, and Pulmonary Systems (R21) - September 8, 2013

PAR-12-172 Translational Research to Improve Obesity and Diabetes Outcome (R18) - March 3, 2015

For more information or to find more funding opportunities, please click here.

PATIENT ORGANIZATION EVENTS

American Association of American Diabetes American Gastroen- American Society for Clinical Endocrinologists Association terological Association Nephrology

Scientific/Clinical Congress Call to Congress Digestive Disease Week Biennial World Congress May 1-5, 2013 May 5-7, 2013 May 18-21, 2013 May 31-June 4, 2013 Phoenix, Arizona Washington, DC Orlando, FL Hong Kong

Click here for more details. Click here for more details. Click here for more details. Click here for more details. Focus on Nephrology, Endocrinology, Page 4 Metabolism, & Gastroenterology

PANDEMIC AND ALL - HAZ ARDS PREPAREDNESS (PAHPA) REAUTHORIZATION ACT U P D A T E S

On March 14, 2013, President Obama signed into law the Pandemic and All-Hazards Preparedness (PAHPA) Re- authorization Act, which reauthorizes the Project BioShield and Special Reserve Fund provisions of PAHPA. The legislation also requires the FDA to develop a formal process for regulatory management plans through which companies can obtain scientific feedback on the development and regulatory review of eligible medical counter- measures (MCMs). In addition, it expanded MCMs to include noninfectious agents, opening the door for biotech companies pursuing products that could be used in national emergencies.

Congress established Project BioShield in 2004 and provided it with 10 years of guaranteed funding. PAHPA was first passed in 2006, and it granted further authority to facilitate BioShield implementation. This legislation es- tablished the Biomedical Advanced Research and Development Authority (BARDA) within HHS to coordinate and fund the acceleration of MCM advanced research and development. Since that time, the government has strate- gically invested in a diverse set of products to treat, diagnose, or prevent a range of pathogens and toxins iden- tified as significant national threats. BARDA awards grants and contracts to develop and purchase medical countermeasures (MCMs), and Project BioShield provides incentives for companies to develop those counter- measures.

The reauthorization of PAHPA demonstrates our nation’s commitment to prioritizing health preparedness and response when confronted by national security issues.

For more information on this legislation, please click here.

FINANCIAL SERVICES L EGISLATION

On February 14, Representative Patrick McHenry (R-NC) introduced H.R. 701, a bill to speed the implementation of Regulation A, a key provision in the Jumpstart Our Business Important Startups (JOBS) Act that will increase access to capital for growing companies, such as Legislation biotech innovators. Dates

BIO supports expeditious and effective implementation of the JOBS Act and efforts to in- R&D Tax Credit centivize and encourage capital formation for emerging biotech companies. Extension

Before the JOBS Act was enacted, Regulation A allowed companies to conduct direct pub- January 1, 2013 lic offerings of up to $5 million; the JOBS Act increased the offering limit to $50 million. Once these changes are implemented, Regulation A will spur fundraising for emerging biotech companies, for which a $50 million capital influx could support groundbreaking research and stimulate job creation. SBIR Final Rule

January 28, Eight of the eleven biotech IPOs since the JOBS Act was signed into law were undertaken by emerging growth companies using the IPO On-Ramp. Other provisions of the JOBS 2013 Act, including a new crowdfunding pathway and reforms to SEC Regulations A and D, are still awaiting rulemaking at the SEC.

PAHPA The JOBS Act provided implementation deadlines for Regulation D (July 4, 2012) and crowdfunding (December 31, 2012). Rep. McHenry’s legislation would add an implemen- March 14, 2013 tation deadline of October 31, 2013 for the Regulation A reforms. Companies cannot take advantage of these capital formation provisions until the SEC Acts. More information on the JOBS Act can be found here.

R&D TAX CREDIT EXTEN SION

On January 1, 2013, Congress passed fiscal cliff legislation which included a year-end tax extenders package that extended the R&D credit through the end of 2013. BIO strongly supports the provisions of this credit and has continued to work to make the credit permanent. To read BIO’s press release, click here. A p r i l 2 0 1 3 Page 5

BIO ENGAGES WITH FED ERAL AGENCIES

BIO Comments on Final SBIR Rule On December 31, 2011, President Obama signed into law a bill reauthorizing the SBIR program through 2017. Included in the reauthorization was an end to the eligibility ban on venture-backed companies. Now, venture- backed companies will be able to compete for 25% of SBIR funds at NIH, NSF, and the Department of Energy and 15% of funds at all other agencies.

When BIO began its advocacy to reform the SBIR program, it had two primary goals: 1) Allow majority venture -backed companies to once again be able to participate in the SBIR program; and 2) Reform the affiliation rules so that SBIR applicants are not affiliated with their investors’ portfolio companies simply on the basis of shared investors and not on any actual mutual control or shared businesses practices.

The SBA published a proposed rule on changes to ownership and affiliation eligibility rules pursuant to the reau- thorization and also released a policy directive to agencies participating in the SBIR program. BIO submitted comments to SBA regarding the policy directive, which can be read here.

On December 27, 2012, SBA published a final rule for determining ownership, affiliation, and size standards. SBA adopted many of BIO’s recommendations on exception for portfolio companies, calculation of stock owner- ship, identify of interest, and newly organized concerns.

The final rule was effective January 28, 2013, and can be viewed here.

BIO Comments on Nasdaq Internal Audit Function Proposal On March 4, Nasdaq filed a proposed rule change with the SEC that would require listed companies to have an internal audit function. The stated goal of the rule is to ensure that listed companies have a mechanism in place to assess their system of internal controls. BIO submitted comments asking the SEC to disapprove the proposed rule, as this requirement would be extremely costly and duplicative with SOX 404(a) and 404(b) for growing biotech companies.

To read BIO’s comment letter, please click here.

NEPHROLOGY/ENDOCRINO LOGY/METABOLISM/ GASTROENTEROLOGY - FOC USED LEGISLATION

S. 452/H.R. 962 - Medicare Diabetes Prevention Act of 2013 This bill would amend title XVIII of the Social Security Act to reduce the incidence of diabetes among Medicare beneficiaries. Sponsor: Sen. Al Franken (MN) Status: Referred to the Senate Committee on Finance

Sponsor: Rep. Susan Davis (CA-53) Status: Referred to the House Committee on Energy and Commerce

H.R. 842 - Functional Gastrointestinal and Motility Disorders Research Enhancement Act of 2013 This bill would expand the research activities of the National Institutes of Health with respect to functional gas- trointestinal and motility disorders, and for other purposes. Sponsor: Rep. James Sensenbrenner (WI-5) Status: Referred to the House Subcommittee on Health

S. 323 - Comprehensive Immunosuppressive Drug Coverage for Kidney Transplant Patients Act of 2013 This bill would amend title II (Old Age, Survivors, and Disability Benefits)(OASDI) of the Social Security Act to extend the months of coverage of immunosuppressive drugs or kidney transplant patients. Sponsor: Sen. Richard Durbin (IL) Status: Referred to the Senate Committee on Finance BIO Meetings and Conferences

BIO Business Forum April 22-25, 2013 Chicago, Illinois

BIO International Convention BIO’S EMERGING April 22-25, 2013 COMPANIES Chicago, Illinois

BIOEquity Europe 2013 May 22-23, 2013 Stockholm, Sweden 1201 Maryland Avenue SW, Suite 900

Washington, DC 20024 BIO World Congress on Industrial Biotechnology Phone: (202) 962-9200 June 16-18, 2013 Montreal, Canada Email: [email protected] BIO CEO & Investor Conference February 10-11, 2014 New York, New York

For more about BIO events, please click here.

MICHAEL J. FOX FOUND ATION FUNDING OPPORTUNITIES

On February 20, 2013, The Michael J. Fox Foundation for Parkinson’s Research (MJFF) launched a series of new funding programs. All programs are open to both academic and industry researchers and the Foundation esti- mates allocating $55 million in 2013 to research programs.

MJFF seeks projects promoting drug development for Parkinson’s disease around exciting therapeutic pathways and targets, including but not limited to programs on alpha-synuclein and LRRK2. Access to MJFF’s growing in- ventory of pre-clinical and clinical tissues and resources to address promising Parkinson’s ideas will also be made available.

More information and application instructions can be found at https://www.michaeljfox.org/research/ apply-for-grant. For questions about how MJFF works with industry, please contact Tracey Mumford, Senior Associate Director of Research Partnerships at [email protected].

To receive email updates about MJFF research programs and other news, write to [email protected].

SEQUESTRATION AND CONTINUING RESOLUTION

Beginning March 1, a series of automatic spending cuts known as sequestration took effect. Of the $1.2 trillion slated to take effect over the next 10 years, $85 billion is scheduled for this year. Across the board cuts for 2013 include the calculated equivalent of a 5.8% cut from the NIH budget and an 8.2% reduction from the FDA budget.

On March 21, the House gave final approval to a continuing funding resolution that outlines spending through the end of the fiscal year, September 30. It ensures that government agencies will stay open after the current funding measure expired on March 27. A broader battle over taxes and spending for the year is still a central topic in Washington and will continue throughout the year.