Deal Watch: Bristol And Otsuka Pursue Oncolytic Virus Therapies Via Licensing Deals

Scrip regularly covers business development and deal-making in the biopharmaceutical industry. Below is a roundup of some of the most noteworthy transactions that occurred between Dec. 12-23. Deal Watch is supported by deal intelligence from Strategic Transactions.

Not only the malls and big box stores were brimming with activity in the days leading up to Christmas, as the biopharmaceutical industry settled into a consistently brisk stretch of deal-making during the two weeks just prior to the holidays. Here is a sampling of that activity:

Second Bristol/PsiOxus Deal Of 2016 Involves Oncolytic Virus Candidate

Bristol-Myers Squibb Co. has linked up with UK oncolytic virus company PsiOxus Therapeutics Ltd. for the second time in six months, this time gaining exclusive worldwide rights to NG-348, a version of PsiOxus’ lead oncolytic virus enadenotucirev, which can be administered intravenously and has been engineered to contain two additional immune-therapeutic transgenes, in a deal potentially worth just under $1bn.

BMS is paying a hefty $50m up front and will be solely responsible for the global development and commercialization of NG-348. [See Deal] If development is successful, the UK biotech could receive up to $886m in development, regulatory and sales-based milestones, as well as royalties on net sales, the companies announced Dec. 20.

PsiOxus has applied “natural selection” pressure on an adenovirus to produce the oncolytic virus, enadenotucirev, that replicates in tumors, but not in healthy human cells, stimulating an inflammatory response that attracts tumor-infiltrating lymphocytes. To give NG-348 a potentially more active warhead against cancer cells, the adenovirus has been modified to contain two genes that activate tumor-infiltrating T-cells in an antigen-specific manner.

The genes code for two membrane-integrated T-cell engaging (MITe) proteins that give both the T-cell receptor (signal 1) and co-stimulatory activation signals; they consist of a membrane anchored full-length human CD80 and a membrane-anchored antibody fragment specific for the T-cell receptor CD3 protein.

This past June, Bristol entered into an exclusive clinical collaboration with PsiOxus to evaluate enadenotucirev in combination with the big pharma’s immuno-oncology agent Opdivo (nivolumab) in the SPICE study, now recruiting patients in the US. Intravenous enadenotucirev given alone is already being evaluated by PsiOxus in the Phase I EVOLVE study. [See Deal] Other companies, including Merck & Co. Inc., are evaluating different combinations of oncolytic viruses with checkpoint inhibitors. (Also see "NICE Clears Amgen’s Imlygic At Second Attempt, Combo Results Keenly Awaited" - Scrip, 9 Aug, 2016.)

Otsuka Links With Takara For Oncolytic Virus

Otsuka Pharmaceutical Co. Ltd. and fellow Japanese company Takara Bio Inc. have entered into a licensing agreement to jointly develop and commercialize in Japan Takara's oncolytic virus candidate HF10 for melanoma, pancreatic cancer and other tumor types.

Otsuka holds exclusive commercialization rights in the country under the Dec. 15 agreement, while Takara will manufacture clinical trial and commercial quantities in return for unspecified fees. [See Deal] Otsuka will pay upfront cash plus development milestone fees totaling around JPY3bn ($25.5m), plus up to two milestone payments based on the attainment of specific sales targets.

HF10 is a spontaneous mutant, attenuated strain of the herpes simplex virus type-1, which is injected into tumors and destroys malignant cells by proliferating inside these. It also induces an immune response that is expected to enhance anti-tumor activity.

Pfizer Targets Tumor-Associated Myeloid Cells In BioInvent Deal

Sweden’s BioInvent International AB has gained Pfizer Inc. as a research collaborator on the development of antibodies to tumor-associated myeloid cells, an emerging field for anticancer drug development, just weeks after the immune-regulatory antibody specialist announced it was ending a Phase II study of the antibody product BI505 in multiple myeloma. (Also see "BioInvent Stumbles In Busy Multiple Myeloma Space" - Scrip, 8 Nov, 2016.)

Pfizer is making a small equity investment in BioInvent, and is being viewed as a strategic partner for the Lund, Sweden-based biotech. BioInvent researchers will collaborate closely with a Pfizer research team based in San Francisco. Pfizer will provide $10m in early payments including an upfront fee, early research funding and a $6m equity investment in new shares of BioInvent at SEK 2.56 ($0.28) per share, a 30% premium to the average volume weighted price in the previous 10 days. [See Deal]

Tumor-associated myeloid cells are part of the innate immune system and are thought to play a role in the resistance of some patients to immuno-oncology agents, and in the process of metastasis. Therapeutic antibodies could reverse the immunosuppressive activity of these tumor-associated myeloid cells, or reduce their number, and their activation may complement T-cell mediated anticancer responses mediated by the adaptive immune system, and the anticancer activity of immune-oncologic agents.

The Pfizer deal is “a testament to our expertise in the field,” BioInvent CEO Michael Oredsson told Scrip.

Milestone payments to BioInvent could add up to $500m if five antibodies reach the market, and further payments would include double-digit royalties on sales, the companies said Dec. 21. BioInvent’s processes “generate so many antibodies to so many targets that we can help in achieving a better understanding of myeloid cell biology, as well as generating therapeutic candidates,” remarked Chief Scientific Officer Björn Frendéus.

Roche And ImmuNext Partner On VISTA Signaling Pathway In Autoimmune Space

New Hampshire-based ImmuNext Inc. announced Dec. 20 that it is collaborating with Roche to develop novel therapies for autoimmune and inflammatory disorders by targeting the V-region immunoglobulin-containing suppressor of T-cell activation (VISTA) pathway. No upfront payment was announced, but the biotech can earn more than $400m in preclinical, development and commercial milestones under the partnership, as well as tiered royalties into the double-digits on sales of any products reaching market.

The deal grants Roche an exclusive, worldwide license to develop and commercialize therapies using ImmuNext’s proprietary technology platform that agonize the VISTA pathway, a negative checkpoint regulator, according to ImmuNext. The two companies will collaborate on preclinical development of candidates that agonize VISTA, which has been shown to limit autoimmune disease in preclinical models.

Based on discoveries by Co-Founder and Chief Scientific Officer Randolph Noelle at Dartmouth College, ImmuNext signed its first deal in 2012, out-licensing preclinical cancer programs to Janssen Biotech Inc.[See Deal]

Circuit And Lundbeck Use Optogenetics For Psychiatric Therapies

Circuit Therapeutics Inc. and H. Lundbeck AS will collaborate on the discovery and development of new treatments for psychiatric disorders. Circuit will apply its optogenetics platform, which activates or inhibits specific neurons using a light-sensitive protein and light source, under the agreement announced Dec. 19. [See Deal]

Different adjustments to wavelengths, location, strengths and colors of the light control the proteins, which initiate cellular signaling cascades to modulate neuron activity. The technology enables better understanding of central nervous system function.

The goal of the deal is to further explore the science surrounding neural circuits associated with psychiatric symptoms and develop medicines to treat them. Circuit, which was founded in 2011, also has two separate optogenetics partnerships with Boehringer Ingelheim GMBH; one in obesity and related metabolic diseases signed last year, and another 2013 research collaboration for psychiatric disorders. [See Deal][See Deal]

Lundbeck's CNS-focused pipeline has several late-phase candidates for psychiatric disorders, including schizophrenia, major depressive disorder and bipolar disorder.

MacroGenics Licenses ADC Linker Technology From Synthon

Synthon BV granted MacroGenics Inc. rights Dec. 12 to its antibody-drug conjugate (ADC) linker technology, which MacroGenics will use in the development of its new cancer candidate MGC018. [See Deal] Synthon agreed to provide manufacturing support and supply the ADC to MacroGenics, and in return gets license fees, milestone payments and royalties.

Synthon’s technology is based on synthetic duocarmycin analogs which, upon binding to the minor groove of DNA, cause irreversible DNA alkylation and tumor cell death. MacroGenics will use the platform to develop MGC018 for solid tumors expressing B7-H3; IND-enabling studies have already begun. The company is working on two other B7-H3 molecules: enoblituzumab, an Fc-optimized mAb against B7-H3, and MGD009, both in Phase I for solid tumors.

ElsaLys Obtains Anti-CD115 Antibody From Its Parent, Transgene

ElsaLys Biotech SAS licensed all development and marketing rights on Dec. 15 to Transgene SA’s immune-oncology candidate TG3003, which it will rename ELB041. [See Deal] ElsaLys was spun out of Transgene in 2013. In exchange for the rights – including rights to sublicense – it pays undisclosed pre-sales milestone fees and royalties. [See Deal]

ELB041 is an anti-CD115 monoclonal antibody that inhibits type 2 macrophages, including and the tumor-associated macrophage (TAM) type M2, which when present in the center of a tumor is highly indicative of poor prognosis. ELB041 has demonstrated preclinical success at lifting immunosuppression mediated by M2 macrophages and inducing antibody-dependent cell-mediated cytotoxicity in the immune system.

ElsaLys has a preclinical proof-of-concept study planned, with Phase I trials in solid tumors anticipated within two years. ElsaLys now has five projects in its pipeline for oncology and ophthalmology indications, including the in-licensed asset.

Arbutus And Spring Bank Sign HBV Trial Collaboration

Spring Bank Pharmaceuticals Inc. and Arbutus Biopharma Corp. entered into a trial collaboration Dec. 19 to investigate the co-administration of Spring Bank’s SB9200 and Arbutus' AB423 for hepatitis B. [See Deal] SB9200 is an oral selective immune-modulator currently in Phase II trials. AB423 is a preclinical HBV capsid assembly inhibitor.

The companies will initially conduct a preclinical study of the SB9200/AB423 combination. AB423 originated at OnCore Biopharma Inc., which merged with Tekmira Pharmaceuticals Corp. in 2015 and became Arbutus. [See Deal]

Orexigen Signs Another Contrave Partnership, For Middle East Markets With Biologix

Orexigen Therapeutics Inc. licensed Biologix FZCo. rights to its obesity drug Contrave (naltrexone/bupropion) in the Middle East on Dec. 19. [See Deal] Territories covered under the agreement are Saudi Arabia, the United Arab Emirates, Kuwait, Oman, Qatar, Bahrain, Lebanon, Jordan, Iraq and Iran.

Biologix is responsible for obtaining regulatory approvals and product registrations and undertaking commercial activities. Orexigen will supply Contrave to Biologix at an agreed transfer price. Biologix anticipates the product could be available in certain countries beginning in the third quarter of 2017. Just last month, Orexigen granted Valeant Pharmaceuticals International Inc. rights to commercialize Contrave in Australia and New Zealand. [See Deal]

Purdue, Shionogi Agree To Co-Promote Symproic

Purdue Pharma LP and Shionogi & Co. Ltd. will co-promote Shionogi's naldemedine as Symproic in the US. Symproic is a peripherally-acting mu opioid receptor antagonist (PAMORA) for opioid-induced constipation (OIC) in opioid-receiving adults with chronic pain (not related to cancer).

Following the conclusion of a pivotal Phase III trial early this year, in which Symproic demonstrated primary and key secondary endpoints in this indication, Shionogi submitted an NDA to the FDA, which accepted it in June 2016 with a target PDUFA date of March 23, 2017. The candidate has a 92% likelihood of approval (3% above average), according to Biomedtracker. Shionogi also submitted an NDA in Japan in March for the treatment of OIC in adults.

Following FDA approval, the partners will jointly launch and commercialize Symproic in the US. The deal leverages Shionogi’s know-how as the developer of naldemedine with Purdue’s expertise in pain therapeutics and presence in the US market. The current collaboration, announced Dec. 19, appears to be an extension of a separate 2006 alliance in which the partners agreed to co-develop and co-promote new therapeutics based on three Purdue undisclosed programs in pain. [See Deal]

You can read more about deals that have been covered in depth in Scrip and other Informa Pharma Intelligence publications in recent days below: