Asia Deal Watch: Daiichi Sankyo Licenses Glycotope's Gatipotuzumab ADC

Daiichi Sankyo gains worldwide rights to an antibody-drug conjugate version of Glycotope’s gatipotuzumab for various cancers. Also, Tasly buys China rights to Mesoblast's CV candidates and India's Cipla grows in Africa.

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

Daiichi Sankyo Signs On For ADC Of Glycotope’s Gatipotuzumab

Daiichi Sankyo Co. Ltd. has acquired exclusive worldwide rights to develop and commercialize an antibody-drug conjugate (ADC) version of Glycotope GMBH’s investigational tumor-associated MUC1-targeting antibody gatipotuzumab.

The Japanese firm will apply its proprietary ADC technology to the glyco-optimized monoclonal antibody (formerly known as PankoMab-GEX), in a move that builds on a previous 2017 option agreement. Glycotope will receive an undisclosed upfront payment under the new deal, announced July 30, and is eligible for clinical, regulatory and sales milestone fees, plus royalties on global sales.

The potentially first-in-class ADC would target the novel carbohydrate-induced conformational epitope, TA-MUC1, providing tumor-specificity given that this is extensively expressed in many cancer types, including ovarian, lung and breast.

Glycotope’s lead clinical program with non-ADC gatipotuzumab is a Phase Ib study in combination with tomuzotuximab, a glyco-optimized second-generation anti-EGFR monoclonal antibody.

The new deal takes to seven the number of novel ADCs in development at Daiichi Sankyo, "which demonstrates our commitment to maximizing the potential of our proprietary ADC payload and linker technology to help address the unmet needs of patients with cancer worldwide," the company’s Antibody Drug Conjugate Task Force head Tom Held noted in a statement.

ADCs deliver their cytotoxic payload inside cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on the cells, and Daiichi Sankyo’s proprietary technology is designed to reduce systemic exposure through cellular targeting.

Other ADCs in the Japanese firm’s pipeline include HER2-targeting DS-8201, in Phase II international development for breast, colorectal, lung and gastric cancer. DS-1062, an anti-TROP2 ADC, and the anti-HER3 asset U3-1402, are in Phase I.

More broadly, Daiichi Sankyo is continuing with a strategic push into oncology – not traditionally one of its focus areas – to find new growth opportunities as it overcomes the loss of patent exclusivity for its long-time top product olmesartan, an antihypertensive.  (Also see "Daiichi Sankyo Lays Out Priorities As It Pursues Oncology Ambitions" - Scrip, 15 Dec, 2016.)

Berlin-based glyco-biology specialist Glycotope also said that it is looking to create "multiple additional formats" based on gatipotuzumab.

Tasly Acquires Chinese Rights To Mesoblast CV Candidates

Tasly Pharmaceutical Co. Ltd. licensed exclusive rights in China on July 17 to develop, manufacture and commercialize Mesoblast Ltd.'s allogeneic mesenchymal precursor cell (MPC) cardiovascular disease candidates MPC150IM and MPC25IC. [See Deal]

Tasly pays $40m up front ($20m in a cash technology access fee and $20m through the purchase of Mesoblast shares at $1.86 each), a $25m milestone fee upon product regulatory approvals in China, six escalating milestone fees upon achievement of certain Chinese sales thresholds, and double-digit escalating royalties on net product sales within its licensed region.

Mesoblast and its existing licensees retain development rights in all other territories. The Australian firm plans to cooperate with Tasly, sharing each other’s clinical trial results in China, the US and other major markets to support respective regulatory submissions for both candidates.

MPC150IM (also known as Revascor) is in Phase III for the treatment or prevention of advanced and late-stage chronic heart failure, a condition characterized by an enlarged heart. The drug is injected directly into the heart muscle, where it releases factors that induce functional cardiac recovery by simultaneously activating multiple pathways. Phase II MPC25IC, also a cellular therapy, is delivered by intracoronary infusion to myocardial infarction patients to protect at-risk heart muscle cells.

Cephalon licensed Mesoblast's MPC-derived therapeutics for degenerative neurological and cardiovascular disease indications in 2010, but later returned the rights to Mesoblast following the former's acquisition by Teva in 2016. [See Deal]

Tasly's deal with Mesoblast comes a week after the Chinese firm's announcement that its Tasly Biopharmaceuticals Co. Ltd. subsidiary will acquire full ownership of its 2010 virus-based immunotherapies joint venture with Transgene Tasly (Tianjin) Biopharmaceutical Co. to gain exclusive Chinese rights to two virus-based candidates, preclinical T601 for solid tumors and Phase I T101 for hepatitis B. [See Deal]

Cipla Accelerates South Africa Push With Mirren Acquisition

Cipla Ltd. has snapped up over-the-counter (OTC) pharmaceutical manufacturer and distributor, Mirren (Pty) Ltd., for R450m ($33.4m), continuing to build momentum for its growth in South Africa.

The deal, routed through the Indian firm’s subsidiary Cipla Medpro South Africa (Pty) Limited, will boost Cipla’s existing OTC portfolio, bringing with it “well-established” Mirren brands such as Broncol Cough, Coryx, Tensopyn and Ultimag, the company said on July 11. Mirren reported revenues of R152m ($11.5m) in fiscal year 2018 compared to R123m ($9.3m) in fiscal 2017.

The deal also is expected to increase Cipla's local manufacturing footprint. Mirren’s website mentions a local factory for the production of oral solids, liquids, granules, powders and specialty creams. Last year, Cipla put large biosimilar manufacturing plans in South Africa on hold following a repositioning of its biotech business.  (Also see "Cipla Cuts Down In-House Biosimilars Plans" - Scrip, 26 May, 2017.)

Mirren said it expects the Cipla transaction to ensure the continued and sustained growth of its brands, but the firm said the well-being of its staff also was an important part of the deal process. The transaction, expected to be completed before Sept. 30, is subject to approval by the Competition Commission of South Africa.

WuXi STA Signs Agreement With Antengene

The WuXi AppTec Inc. subsidiary STA Pharmaceutical said on July 20 it entered a partnership with drug developer Antengene Corp. to build chemistry, manufacturing and control (CMC) expertise around a group of innovative oncology drugs. STA will provide end-to-end solutions for process R&D and manufacturing from the preclinical to commercial stages, making use of China’s Manufacturing Authorization Holder (MAH) scheme to help accelerate new drug development.

Shanghai-based Antengene focuses on the development of novel new drugs in China and the Asia-Pacific region through both internal R&D and external licensing partnerships. Its pipeline includes several clinical-stage drug candidates in oncology and viral infections. Antengene licensed rights in Asia from Karyopharm Therapeutics Inc. in May for four drug candidates, mostly in oncology.  (Also see "Deal Watch: Allergan, Celgene, AstraZeneca Among Biopharmas Advancing Existing Partnerships" - Scrip, 24 May, 2018.)

The STA collaboration will focus initially on clinical-stage assets, starting with Antengene’s Phase II/III candidate ATG-008, but will be expanded to other pipeline projects, including drugs for solid tumors, hematological malignancies and viral infections.

ATG-008, an oral mTOR kinase (TORC1/2) inhibitor, is in a multi-regional clinical trial (TORCH) for hepatitis B virus-positive advanced hepatocellular carcinoma patients, for which enrollment has just started at sites in China, Taiwan and South Korea. The drug is being developed in 14 Asian markets under a partnership with Celgene Corp., which in April 2017 acquired an equity stake in Antengene as part of the companies' agreement.  (Also see "China Investment Roundup: Spotlight On Oncology" - Scrip, 31 Oct, 2017.)

Antengene’s pipeline now includes five clinical-stage products, including ATG-101 for relapsed/refractory multiple myeloma, lymphomas and solid tumors; ATG-016 and ATG-019 in multiple cancer types; and ATG-527, an antiviral for influenza, respiratory syncytial virus and Epstein-Barr virus diseases.

Under China’s MAH scheme, first rolled out in pilot form in 2015, a company commercializing a drug manufactured in China is allowed to use an external contract partner for production, rather than having to operate their own in-house plant as required under previous regulations.

Takeda Taps HiFiBiO's Single-Cell Screening Platform

Takeda Pharmaceutical Co. Ltd. and HiFiBiO Therapeutics said on July 30 that they entered into an agreement under which the companies' scientists will collaborate on the discovery of antibody therapeutics against Takeda's targets for gastrointestinal diseases, cancer and other disorders. Financial details were not disclosed, but HiFiBiO will receive upfront, R&D, milestone and royalty payments.

HiFiBiO operates from facilities in Cambridge, Mass., Paris and Shanghai. The company emerged from lab space in investor Nest.Bio's incubators in Cambridge, Mass. and Hangzhou, China with a $37.5m Series B venture capital round in May. (Also see "Finance Watch: Early-Stage Firms Gain Deal-Making Insight As Golumbeski Joins VC Ranks" - Scrip, 21 May, 2018.) 

Its technology platform for antibody discovery through single-B-cell screening and analysis will be used in the Takeda partnership. Takeda will be responsible for preclinical and clinical development of antibodies discovered by its scientists working with HiFiBiO's researchers.

I-Mab, ABL To Collaborate On Bispecific Antibodies

Shanghai-based I-MAB Biopharma and South Korea's ABL Bio Corp. announced on July 26 that ABL will pay up to $100m in licensing and other fees to obtain global rights, excluding greater China, for I-Mab's bispecific antibodies against undisclosed targets. The companies will also  collaborate on the development of additional bispecific antibodies.

ABL will pay $2.5m up front and I-Mab is entitled to R&D and sales milestone fees for the licensed bispecifics that will bring total consideration to $100m, plus payment of royalties on net sales. I-Mab and ABL will share development costs and rights in China, South Korea and the rest of the world – in various configurations for the different territories – for three more bispecific antibody programs.

I-Mab is focused on antibody development for immuno-oncology and immunology indications, but the ABL deal appears to be focused on immuno-oncology programs. I-Mab has in-licensed assets from MorphoSys AG and Genexine Inc. to build its portfolio of drugs its will develop for the China market. (Also see "Genexine Seals I-O Licensing Deal With I-Mab, Builds Momentum" - Scrip, 26 Dec, 2017.) The deal with ABL is its second out-licensing agreement.

I-Mab, which was created through the merger of Third Venture Biotech and Tasgen Bio, raised a $150m Series B round in 2017 and a $220m Series C in June.  (Also see "Venture Funding Deals: I-Mab Is The Mega-Round Leader With $220m Series C" - Scrip, 5 Jul, 2018.)

ABL closed a $65m Series C this year – its third VC round since it launched in 2016. The company is developing antibody therapies for immuno-oncology indications and neurodegenerative diseases. (Also see "Interview: Fledgling ABL Bio And Its Global Ambitions In Bispecific Antibodies" - Scrip, 17 Aug, 2017.) ABL recently out-licensed global rights for five cancer product candidates to TRIGR Therapeutics. (Also see "Deal Watch: BioCryst Shareholder Dissent Scuttles Planned Merger With Idera" - Scrip, 13 Jul, 2018.)

Genexine's IO Therapies Selected By Projects Supported By Korean Govt Entities

Genexine Inc. said on Aug. 2 that GX-188E, an HPV therapeutic DNA vaccine, has been selected as a project to be supported by National OncoVenture, a Korean government-funded oncology drug development program.

The two will initially co-develop GX-188E until early Phase II clinical trials to test safety and efficacy of the therapy in cervical cancer patients who can't undergo surgeries or don't respond to standard therapies.

GX-188E, currently being developed in Phase II clinical trials, is an HPV therapeutic DNA vaccine for cervical intraepithelial neoplasia (CIN) and HPV-induced cancers caused by persistent infection by high-risk HPV types 16/18. A Phase I study demonstrated that GX-188E, a rationally designed HPV DNA vaccine to target HPV antigens preferentially on dendritic cells, elicited significant E6/E7 specific IFN-γ-producing T-cell responses in all CIN3 patients when administered intramuscularly by electroporation. Seven out of nine patients had complete regression of their CIN3 lesions, viral clearance, and exhibited enhanced antigen-specific polyfunctional CD8 T-cell responses within 36 weeks of follow-up. These results were published in October 2014 in Nature Communications.

Genexine has recently received an IND approval from South Korea's Ministry of Food and Drug Safety to initiate a Phase Ib/II trial of GX-188E in combination with Merck & Co. Inc.'s Keytruda (pembrolizumab), an anti-PD-1 therapy already approved for treatment of patients with HPV-induced advanced non-resectable cervical cancer, among other uses. 

The Korean biotech also announced on July 18 that Hyleukin-7, its investigational T-cell amplifier, has been selected for inclusion in the Korea Drug Development Fund (KDDF)’s joint R&D program with MSD. 

With the support of a KDDF grant and participation from NeoImmuneTech Inc., Genexine's spin-off company in the US, Genexine will conduct a Phase Ib/II clinical trial to investigate the safety and efficacy of Hyleukin-7 treatment in combination with Merck’s Keytruda in patients with triple-negative breast cancer.

"If successful, we believe this collaboration with Merck will give more clinical evidence for Hyleukin-7’s potential ability to reconstitute and reinvigorate the anti-tumor T-cell immunity in TNBC patients, who tend to show relatively low response rates and poor survival for a checkpoint inhibitor treatment," said Genexine’SVP, Head of Development Division, Jungwon Woo. “This collaboration will allow us to progress quickly in the clinic as a part of robust examination of Hyleukin-7’s broad applicability.”

GC LabCell, AbClon To Co-Develop Anti-Cancer CAR-NK Cell Therapies

GC LabCell, an affiliate of GC Pharma Group, and AbClon said on Aug. 1 that they agreed to co-develop next generation immuno-oncology therapies using chimeric antigen receptor-natural killer (CAR-NK) cells.

At present, the core technology of CAR-NK cell immuno-oncology therapies has been focused on development of antibodies that recognize target disease proteins. However, AbClon has a platform technology that draws effective antibody drug candidates via development of antibodies that bind various parts of disease proteins.

GC LabCell is progressing a Phase II study of anti-cancer NK cell therapy MG4101 (allogeneic NK cell) for hepatocellular carcinoma, which is said to be the closest to commercialization of anti-cancer NK cell therapies worldwide.

MedPacto In Clinical Tie-Ups With MSD, AstraZeneca To Evaluate Vactosertib

MedPacto Inc., a subsidiary of TheragenEtex, said on July 24 that it has entered into a clinical collaboration agreement with Merck Sharp & Dohme Ltd. to evaluate the safety and efficacy of vactosertib (TEW-7197), MedPacto’s investigational oral inhibitor of TGF-β type I receptor (TGFBRI), in combination with Merck’s anti-PD-1 therapy Keytruda in patients with metastatic or locally advanced colorectal (mCRC) and gastric cancer/gastroesophageal junction adenocarcinoma (GC/GEJC).

Under the agreement, MedPacto will conduct a Phase 1b study to establish the safety and dose of the combination agents. Following the identification of a recommended dose, MedPacto plans to initiate a Phase IIa study to explore the efficacy of the combination in mCRC and GC/GEJC. The trial, expected to be initiated the second half of 2018 and completed within two years, will be conducted in several sites in South Korea, including Asan Medical Center, National Cancer Center and Samsung Medical Center.

“The revitalization of TGF-β for drug development further reinforces the importance of this pathway. We believe that vactosertib’s immuno-modulatory role in combination with Keytruda is very promising for increasing responses in mCRC and GC/GEJC,” said Seong-Jin Kim, founder and CEO of MedPacto.

Vactosertib is a potent and highly selective, orally available inhibitor of TGF-β type I receptor to block the SMAD-mediated and non-canonical TGF-β signaling pathway. TGF-β inhibition enables immune infiltration to confer susceptibility to immuno-oncology therapies for treatment of cancers that grow in TGF-β rich environment. Vactosertib was proven to be safe and well-tolerated in a Phase I study conducted in the US. It is currently being evaluated in Phase Ib/IIa trials to treat a variety of solid tumors and hematological malignancies including gastric cancer, pancreatic cancer, desmoid sarcomas, myelodysplastic syndrome and multiple myeloma.

Separately, MedPacto also announced on July 24 a clinical collaboration with AstraZeneca PLC to evaluate the safety and efficacy of  vactosertib in combination with AstraZeneca's PD-L1 inhibitor Imfinzi (durvalumab) in patients with metastatic non-small cell lung cancer (NSCLC).

MedPacto and AstraZeneca will collaborate on a non-exclusive basis to evaluate the combination of the two drugs in NSCLC. MedPacto expects to initiate a Phase Ib/IIa study in the second half of 2018 to establish the safety and efficacy of vactosertib in combination with durvalumab. MedPacto will sponsor and fund the study and AstraZeneca will supply durvalumab for the study. The trial will be conducted in several sites in South Korea including Yonsei Severance Hospital and National Cancer Center and is expected to be completed within two years.