Licensing and Development Agreement for IMP731 for Immune Diseases

Dealdoc

Licensing and development agreement for IMP731 for immune diseases

Immutep GlaxoSmithKline PRIMA BioMed

Jan 06 2011

Immutep Companies: GlaxoSmithKline PRIMA BioMed Announcement date: Jan 06 2011 Deal value, US$m: 100 : sum of upfront and milestone payments

• Details

• Financials

• Termsheet

• Press Release

• Filing Data

• Contract

Details

Announcement date: Jan 06 2011 Bigpharma Industry sectors: Biotech Compound name: IMP731, GSK2831781 Compound Asset type: Technology Gastrointestinal » Inflammatory bowel disease » Ulcerative colitis Therapy areas: Immunology Immunology » Other autoimmune Technology types: Antibodies » Monoclonal antibodies Development Deal components: Licensing Stages of development: Phase II Geographic focus: Worldwide

Financials

Deal value, US$m: 100 : sum of upfront and milestone payments Upfront, US$m: n/d : upfront payment 5 : related to the first patient being dosed in GSK’s Phase II clinical trial Milestones, US$m: evaluating GSK2831781 in ulcerative colitis n/d : milestone payments Royalty rates, %: n/d : single digit tiered royalties Funding, US$m: n/d : development costs

Termsheet

September 2019

Immutep will receive a milestone payment from GSK of £4 million (~US$5.02 million) related to the first patient being dosed in GSK’s Phase II clinical trial evaluating GSK2831781 in ulcerative colitis.

January 2015

Prima BioMed announced the first dosing of a subject by GSK in a Phase 1, first - in - human clinical trial of a novel depleting anti - LAG - 3 antibody (GSK2831781) for the treatment of autoimmune diseases.

© 2009-2021, Wildwood Ventures Ltd. All rights reserved. The first subject dosing in the Phase 1 trial triggers a n undisclosed single digit million dollar financial milestone payment to Immutep from GSK, which licensed the depleting anti - LAG antibody technology from Immutep in 2010.

This first milestone payment from GSK also triggers a milestone payment to the sellers of Immutep, as part considerati on for the acquisition price.

6 January 2011

Immutep has a licence agreement granting GSK exclusive worldwide rights to ImmuTune IMP731 and any other antibodies that deplete LAG-3 positive cells.

GSK will assume all development responsibility and associated costs for IMP731.

Immutep will receive an upfront payment and milestones of up to GBP 64 million (USD 100 million) and is eligible for single-digit, tiered royalties if all objectives are achieved.

Press Release

September 2019

Immutep to Receive £4M Milestone Payment From GSK

SYDNEY, Australia, Sept. 23, 2019 (GLOBE NEWSWIRE) -- Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep“ or “the Company”), a biotechnology company developing novel immunotherapy treatments for cancer and autoimmune diseases, announces that it will receive a milestone payment from GSK of £4 million (~US$5.02 million) related to the first patient being dosed in GSK’s Phase II clinical trial evaluating GSK2831781 in ulcerative colitis.

GSK2831781 is derived from Immutep’s IMP731 antibody, a depleting anti-LAG antibody technology that was exclusively licensed to GSK. Under the terms of the agreement, Immutep is eligible to receive up to £64 million (~US$ 80.38 million) in developmental milestone payments as well as single-digit tiered royalties, if GSK2831781 is commercialized. GSK is responsible for all costs associated with the clinical development and commercialization of GSK2831781.

Immutep CEO Marc Voigt, said: “It is very encouraging to see GSK advancing their product candidate in a phase II clinical trial for ulcerative colitis, further validating LAG-3 as a potential target for therapeutics in autoimmune diseases. These partner milestone payments are an important source of nondilutive funding to the Company and this capital will be deployed to further advance our extensive development programs.”

Further details of the Phase II GSK trial can be found at: https://clinicaltrials.gov/ct2/show/NCT03893565?term=GSK2831781&rank=1

About IMP731 and GSK2831781 GSK2831781 is a depleting anti-LAG antibody that was derived from IMP731 and was licenced to GSK in 2010.

IMP731 and GSK2831781 are designed to specifically deplete potentially pathogenic, recently activated LAG-3 expressing T cells which are enriched at the disease site in T cell driven immuno-inflammatory disorders and should spare other T cells which may be necessary for other functions.

About Immutep

Immutep is a globally active biotechnology company that is a leader in the development of immunotherapeutic products for the treatment of cancer and autoimmune disease. Immutep is dedicated to leveraging its technology and expertise to bring innovative treatment options to market for patients and to maximise value to shareholders.

Immutep’s current lead product candidate is eftilagimod alpha (“efti” or “IMP321”), a soluble LAG-3Ig fusion protein based on the LAG-3 immune control mechanism. This mechanism plays a vital role in the regulation of the T cell immune response. Efti is currently in a Phase IIb clinical trial as a chemoimmunotherapy for metastatic breast cancer termed AIPAC (clinicaltrials.gov identifier NCT02614833); a Phase II clinical trial referred to as TACTI-002 (Two ACTive Immunotherapies) to evaluate a combination of efti with KEYTRUDA® (pembrolizumab an anti-PD-1 therapy) in several different solid tumours (clinicaltrials.gov identifier NCT03625323); a planned Phase I clinical trial referred to as INSIGHT-004 to evaluate a combination of efti with avelumab (clinical trials.gov identifier NCT03252938); and a Phase I combination therapy trial in metastatic melanoma termed TACTI-mel (clinicaltrials.gov identifier NCT02676869).

Additional LAG-3 products, including antibodies, for immune response modulation in autoimmunity and cancer are being developed by Immutep’s large pharmaceutical partners. Immutep is also developing an agonist of LAG-3 (IMP761) for autoimmune disease.

Immutep is listed on the Australian Securities Exchange (IMM), and on the NASDAQ (IMMP) in the United States.

Prima Biomed (PRR.AX) Release: Financial Milestone Payment To Be Received From GlaxoSmithKline (GSK)

Prima BioMed Ltd (ASX: PRR; NASDAQ: PBMD) (“Prima”, the “Company”) announces the first dosing of a subject by GSK in a Phase 1, first - in - human clinical trial of a novel depleting anti - LAG - 3 antibody (GSK2831781) for the treatment of autoimmune diseases.

Prima’s CEO, Marc Voigt , said the beginning of the Phase 1 trial is a significant milestone for the Company, following its recent acquisition of Immutep, which is now a 100% owned subsidiary of Prima.

“The first subject dosing in the Phase 1 trial triggers a n undisclosed single digit million dollar financial milestone payment to Immutep from GSK, which licensed the depleting anti - LAG antibody technology from Immutep in 2010 . Importantly , the partnership with GSK gives rise to significant further potential mil estone payments as well as additional royalties . Under the terms of the 2010 agreement, GSK has responsibility for all development and associated costs for GSK2831781 . Immutep received an upfront payment and potential future milestones totalling up to £64 million ( approximately A $1 18 million) and is eligible for single - digit, tiered royalties if all objectives are achieved. ” Mr Voigt said.

This first milestone payment from GSK also triggers a milestone payment to the sellers of Immutep, as part considerati on for the acquisition price.

T he randomised, double blind Phase 1 trial aims to investigate the safety, tolerability and pharmacokinetics of GSK2831781 . A total of approximately 63 subjects will be treated and receive either placebo or GSK2831781 . Recruitment for the trial is currently underway and further information may be obtained at https://clinicaltrials.gov/ct2/show/NCT02195349?term=gsk+lag+3&rank=1 clinicaltrials.gov .

About IMP731 and GSK2831781

GSK2831781 is an anti - LAG3 antibody derived from IMP731 originally developed by Immutep. GSK licensed the development r ights to the IMP731 antibody technology from Immutep in December 2010 .

IMP731 and GSK2831781 are designed to specifically deplete potentially pathogenic, re cently activated LAG - 3 expressing T - cells which are enriched at the disease site in T - cell drive n immuno - inflammatory disorders and should spare other T - cells which may be necessary for other functions.

About Prima BioMed

Prima BioMed is a globally active biotech company developing immunotherapeutic products for the treatment of cancer. Prima is dedicated to leveraging its technology and expertise to bring innovative treatment options to market for patients and to maximize value for its shareholders. Following the acquisition of Immutep, Prima owns a number of different immunotherapy products in p reclinical and clinical development. www.primabiomed.com.au

January 2011

Immutep S.A. and GlaxoSmithKline (GSK) Sign Licence Agreement for IMP731, a Novel Therapeutic Antibody for the Treatment of Autoimmune Diseases

6 January 2011

Orsay, France, January 6th, 2011 - Immutep S.A. announced today the execution of a licence agreement granting GSK exclusive worldwide rights to ImmuTune(R) IMP731 and any other antibodies that deplete LAG-3 positive cells. IMP731 has demonstrated potency at low doses in preclinical models of T-cell mediated inflammation and could represent a new therapeutic approach to the treatment of autoimmune disease.

Under the terms of the agreement, GSK will assume all development responsibility and associated costs for IMP731. Immutep will receive an upfront payment and milestones of up to GBP 64 million (USD 100 million) and is eligible for single-digit, tiered royalties if all objectives are achieved.

“We are very pleased to hand over the development of IMP731 to GSK, with its commitment to bringing breakthrough therapies to patients,” said John Hawken, CEO. “For Immutep, the value created through this transaction will enable us to focus our resources on advancing our oncology assets, IMP321 and IMP701. IMP321 is ready for a Phase IIb/III trial in the chemo-immunotherapy of first-line metastatic cancer.”

IMP731 is a cytotoxic antibody that depletes activated T-cells. Chronically activated T-cells are a major component in many autoimmune diseases. LAG-3 (Lymphocyte Activation Gene-3) is a marker for activated long-lived effector-memory T-cells. Deleting activated pathogenic T-cells rather than simply blocking one of their functions (for example production of TNF-a, IL-6, IL-23) is a new therapeutic approach.

In addition, selective depletion of these pathogenic LAG-3+ T-cells will lead to targeted immunosuppression (i.e. only a subset of activated T-cells will be suppressed, not all T-cells as with corticoids or cyclosporin). This very specific long-lived immunosuppression should lead to higher therapeutic indices compared to classical immunosuppressive agents, with a reduced risk of increased susceptibility to infectious agents,

Overall, such a targeted therapy, inducing long-term effects with a minimum number of injections is a promising approach in the many autoimmune diseases where self-antigens have activated T-cells, for example, rheumatoid arthritis and multiple sclerosis.

Cabinet Luc Barny acted as legal advisor to Immutep.

For further information please visit the website http://www.immutep.com

ImmuTune(R) IMP731 – depleting antibody Lymphocyte-Activation Gene-3 (LAG-3, CD223) is a marker for recently activated effector T cells. During inflammation LAG-3 is strongly upregulated and plays an important role in antigen-presenting cell (APC) activation. Relatively few molecules have been identified as sustained in vivo T-cell activation markers in human. IMP731 is an IgG1 antibody specific for the LAG-3 antigen, which has been shown to deplete LAG-3 positive cells by antibody mediated cell mediated cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC).

Activated T-cells and autoimmune disease Activated T lymphocytes are of major importance in many autoimmune diseases. Therefore specifically depleting LAG-3+ T-cells will lead to targeted immunosuppression that will spare resting T-cells while eliminating pathogenic activated T-cells. It has previously been shown that anti-LAG-3 depleting antibodies inhibit heart allograft rejection in rats (Haudebourg et al, Transplantation 2007). In a second study, a cytotoxic LAG-3 chimeric antibody (IMP731) was shown to be a selective therapeutic depleting agent in a non-human primate model of T-cell mediated inflammation. Depletion of LAG-3+ T lymphocytes resulted in a long-lasting inhibition of immune responses.

These preclinical studies were carried out in collaboration with Bernard Vanhove and Gilles Blancho's teams in the Inserm unit U643 at the University of Nantes, France.

Selectively deleting activated T lymphocytes represents a promising therapeutic approach as an alternative to current immunosuppressive treatments in autoimmunity providing a competitive advantage by targeting only pathogenic T-cells that are specific for auto- or allo-antigens without modifying the protective immunity directed against third party antigens.

Inserm U643 The INSERM UMR 643 is hosted in the ITUN (Institut de Transplantation, Urologie, Néphrologie) at the Nantes University Hospital. The area of research of INSERM UMR 643 covers transplantation science and immunosuppression/tolerance. The aim is to analyze and inhibit immune responses mainly in organ and cellular transplantation. Immune-mediated kidney diseases, autoimmune diseases and gene therapy in which immune responses are of prime importance are also investigated.

Immutep S.A. Immutep S.A. is a biopharmaceutical company developing immunostimulatory factors for the treatment of cancer and chronic infectious diseases and immunomodulatory therapeutic antibodies for the treatment of cancer or autoimmune disease. The Company's technologies are based on the LAG-3 immune control mechanism that mediates T-cell immune responses. Apart from the depleting antibody, IMP731, described above, two of the Company's other products are:

ImmuFact(R) IMP321 IMP321 is an APC (antigen presenting cell) activator that has completed a Phase I/II clinical trial combined with chemotherapy (chemo-immunotherapy) in first-line metastatic breast cancer. The trial showed a doubling of the clinical response rate compared to paclitaxel alone and a correlation with patient monocyte counts. Three Phase I/II clinical trials are in progress: in pancreatic cancer combining IMP321 with gemcitabine in chemoimmunotherapy, a disease-free melanoma study with IMP321 as a therapeutic vaccine adjuvant to peptide antigens and a lympho-depletive/adoptive transfer metastatic melanoma study.

ImmuTune(R) IMP701 IMP701 is an antagonist anti-LAG-3 antibody. It gives rise to T-cell proliferation in a similar manner to anti-CTLA-4 and anti-PD-1 antibodies. The development of a human version for clinical trials is in progress.

Filing Data

Not available.

Contract

Not available.