Deal Watch Asia Focus: Pfenex Licenses Asian Rights To Forteo Copy To NT Pharma Group

Otsuka obtains Japanese rights to two cancer gene therapy candidates from Takara. GlaxoSmithKline extends its protein degradation collaboration with Kymera.

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.

NT Pharma Gains Asian Rights To Pfenex’s Forteo Equivalent

Pfenex Inc. has granted China's NT Pharma Group Company Limited non-exclusive development and exclusive commercialization rights to its osteoporosis treatment PF708 in Mainland China, Hong Kong, Singapore, Malaysia and Thailand. Pfenex’s lead product candidate, PF708 is a therapeutic equivalent candidate to Lilly Research Laboratories's Forteo (teriparatide), and was developed using Pfenex’s proprietary Expression Technology platform.

Under the deal announced April 18, Pfenex received $2.5m upon signing of the agreement and could receive additional payments of up to $22.5m in development, regulatory and sales-related milestones, along with double-digit royalties on net product sales.

NT Pharma, which has an existing integrated branded and generic business across oncology, orthopedics, central nervous system, hepatology and respiratory, will be responsible for any further development required to achieve regulatory approvals, and commercialization activities, in its territories. Its orthopedic franchise already includes Miacalcic (salcatonin), acquired from Novartis AG. Pfenex CEO Eef Schimmelpennink said the new alliance would build on NT Pharma’s demonstrated experience in the space.

The firms also hinted that the tie-up could be expanded in the future, with NT Pharma Chairman and CEO Ng Tit saying the partnership would “open further discussion on potential partnering for other Pfenex pipeline product candidates."

Pfenex is developing a broad range of therapeutic equivalents, vaccines and biologics, along with novel anthrax vaccine candidates, hematology/oncology products including recombinant crisantaspase, and biosimilar candidates ranibizumab and pegfilgrastim.

Otsuka Gets Pair Of Gene Therapy Candidates From Takara

Otsuka Holdings Co. Ltd. has acquired co-development and exclusive sales rights in Japan to two gene therapy products being developed by Takara Shuzo Co. Ltd. for oncology applications, in a deal announced April 9 that will build on an earlier alliance between the two Japanese firms.

Under the new tie-up, Takara will be responsible for manufacturing and quality aspects of the therapies, NY-ESO-1 siTCR (TBI-1301, TBI-1301-A) and CD19 CAR (TBI-1501), while Otsuka will conduct all required clinical studies, regulatory submissions, and sales and safety data-collection activities. All potential indications for the therapies in cancer are covered by the agreement, which also gives Otsuka right of first refusal to the products in nine Asian countries outside Japan.

Detailed financial terms were not disclosed, but Takara will be eligible for total upfront and milestone payments of around JPY6.3bn ($58.9m), tied to specific development targets, along with payments for product supply. Milestones will also be payable on certain target sales for NY-ESO-1 siTCR, along with running royalties on net sales.

The therapy recently was given “sakigake” (priority review) status in Japan, enabling expedited review and potentially early market access. T-cell receptors (TCRs) recognize the NY-ESO-1 tumor antigen, and the therapy is transduced ex vivo to patients’ T-cells, using a proprietary technique and siTCR vector to mimic the expression of endogenous TCRs. The treated cells are then expanded and infused back to the patient.

NY-ESO-1 siTCR is currently in a Phase I/II program in Japan for synovial sarcoma, which has uniformly high NY-ESO-1 antigen expression. The CD19 CAR therapy targets the CD19 antigen expressed on lymphoma B-cells in acute lymphoblastic leukemia (ALL), and uses similar transduction and infusion processes. Phase I/II trials in adult ALL are also underway in Japan.

The two companies are already working together under a December 2016 deal to develop Takara’s oncolytic virus HF10, an attenuated strain of herpes simplex-1, for cancer indications including melanoma and pancreatic cancer, which Otsuka will commercialize in Japan. [See Deal]

GSK Extends Protein Degradation Interest With Kymera Deal

Research into what is being heralded as a new therapeutic modality, the targeted degradation of disease-causing proteins, by Kymera Therapeutics LLC has attracted the UK-based pharma GlaxoSmithKline PLC into a two-year drug discovery collaboration.

Kymera is working on E3 ligases, enzymes which are part of the cell's innate protein degradation and recycling machinery, which mark proteins for destruction by the ubiquitin-proteasome system. GSK and Kymera will evaluate a limited number of protein-degradation targets to discover novel drug candidates, and will collaborate on the discovery of novel E3 ligases, the companies said April 4.

Kymera designs heterobifunctional molecules that bring dysregulated proteins to the attention of E3 ubiquitin ligases, causing ubiquitination of the target protein, and degradation. There are more than 600 E3 ligases, and only a handful of E3 ligase ligands have so far been identified by researchers. GSK has been interested in protein degradation for some time – it set up a research unit dedicated to protein degradation in 2012, Kymera notes.

Other big pharma companies are also taking an interest in ubiquitin-proteasome system research as a source of new therapies, including Celgene Corp. in its recent deals with Prothena Corp. PLC and Vividion Therapeutics Inc.. (Also see "Celgene Further Commits To Neuroscience With Prothena Pact " - Scrip, 21 Mar, 2018.) Genentech Inc. has expanded its collaboration with Arvinas Inc. in the protein degradation field as well, (Also see "Deal Watch: Genentech Expands Upon Arvinas PROTAC Collaboration" - Scrip, 15 Nov, 2017.) while other firms active in the field include Mission Therapeutics Ltd and C4 Therapeutics Inc. (Also see "C4 And Google's Calico Enter Mysterious Alliance On 'Diseases Of Aging'" - Scrip, 24 Mar, 2017.)

Corporate investors are also taking an interest in the potential new approach to drug candidates: Kymera raised $30m in a Series A round six months ago that included Atlas Venture, Lilly Ventures and Amgen Ventures as investors. (Also see "Finance Watch: NDA-Ready Impact Gets Commitment For Another $90m" - Scrip, 30 Oct, 2017.)

Helsinn Partners With Glenmark For First Licensing Deal In India

Helsinn Group has inked an exclusive licensing pact with Glenmark Pharmaceuticals Ltd. for its combination anti-emetic, Akynzeo (netupitant/palonosetron) – the first such deal for the Swiss cancer care products group in India.

Glenmark gets exclusive marketing rights to Akynzeo in India and Nepal; the product has already received marketing approval from India’s Central Drugs Standard Control Organization (CDSCO), the company said April 4. Privately held Helsinn expects Glenmark’s “renowned expertise” in sales, marketing and distribution in the region to take Akynzeo to more patients in India and Nepal.

An oral fixed combination of netupitant 300mg and palonosetron 0.5mg in capsule form, Akynzeo is used for prevention of chemotherapy-induced nausea and vomiting (CINV). Helsinn is also studying NEPA [netupitant/palonosetron] I.V. versus NEPA oral for the prevention of CINV in women with breast cancer. SC100634

Akynzeo is marketed in the EU, the US and several other markets. Helsinn currently has 20 licensing partners for the product in 167 countries; the Swiss firm’s business model is structured around in-licensing innovative products, taking these through the full clinical development program and commercialization directly or via partners. Last month, it acquired worldwide rights to Valchlor/Ledaga, (mechlorethamine/chlormethine) from Actelion Pharmaceuticals Ltd. (Also see "Deal Watch: Opportunity Knocks For Partnerships In Asia" - Scrip, 27 Mar, 2018.)

Glenmark too appears to be building on its in-licensing efforts. In February, it launched Nourkrin Woman, a proteoglycan replacement formula for normalizing hair growth cycle (licensed from the Denmark-headquartered Pharma Medico), while in January it introduced a biosimilar of adalimumab (licensed from Zydus Cadila).

CKD Ties Up With US Pharma To Sell Biosimilar In Japan

Chong Kun Dang Pharmaceutical Corp. (CKD) said April 16 that it has agreed to export CKD-11101, a biosimilar version of second-generation EPO product NESP/Aranesp (darbepoetin alfa), to a US pharma firm's Japanese unit.

The latest deal, which includes exports of anemia therapy CKD-11101, will grant the licensee the exclusive right to conduct clinical trials for regulatory approval in Japan as well as to sell the product in the country. Identity of the US pharma firm and size of the deal weren't disclosed due to a confidentiality agreement.

Chong Kun Dang will receive upfront and milestone payments as well as sales royalties once the product is launched. The South Korean pharma has filed for regulatory approval for CKD-11101 in South Korea with a goal to receive regulatory approval this year and launch the product in the country in April 2019 as the world's first NESP biosimilar.

The latest deal for "the Japanese market worth KRW470bn ($442m) will be a stepping stone [for the company] to enter the global NESP market worth KRW2.8tn," said the company in a statement. "Beginning with CKD-11101, we will develop various biologics going forward."

Aside from CKD-11101, Chong Kun Dang is developing biosimilars of long-acting protein and antibody drugs as well as novel biologics. It is progressing a preclinical trial withCKD-701, a biosimilar version of Lucentis (ranibizumab), and innovative drug candidate CKD-702, a preclinical bispecific antibody drug candidate, which is said to overcome tolerance and weakness of existing targeted cancer therapies.

You can read more about deals that have been covered in depth by Scrip in recent days below:

(Also see "Sweet Enough? Takeda Raises, Adds Cash To Shire Offer " - Scrip, 22 Apr, 2018.)	Takeda Pharmaceutical Co. Ltd. has further bumped up its offer for acquisition target Shire PLC, raising the per share price and cash component, in what the Japanese firm says is a “compelling” proposal worth well over $60bn. Will it be fourth time lucky?
(Also see "Shire Rejects Multiple Equity-Loaded Takeda Offers, Allergan Declines To Bid" - Scrip, 19 Apr, 2018.)	Takeda's most recent offer for Shire had an estimated total value of $61bn, but likely included too much equity and too little cash. The companies continue negotiating as an April 25 deadline looms, while Allergan PLC stated it won't bid for Shire.
(Also see "Eisai Primes Push For Biogen MS Range In India" - Scrip, 12 Apr, 2018.)	Eisai Co. Ltd. is straddling a mix of new opportunities for growth in India as it takes charge of sales of Biogen Inc.’s multiple sclerosis portfolio in the country and also eyes potential gains from its Japanese parent’s recent deal with Nichi-Iko Pharmaceutical Co. Ltd..
(Also see "Mylan Looks To Expedite Biosimilar Humira in EU Through Kyowa Deal " - Scrip, 12 Apr, 2018.)	Mylan NV has acquired commercial rights in Europe to Kyowa Hakko Kirin Co. Ltd.n's biosimilar adalimumab, paving the way to an early market entry through the product, which could be approved in the second half of this year. But might there be a shift in the commercialization outlook for its partnered adalimumab with Biocon Ltd.?
(Also see "Shire's Suitors: Takeda, Pfizer Seen As Likely To Bid; Amgen Could Enter Fray" - Scrip, 6 Apr, 2018.)	Takeda indicates to analysts that it is warming to idea of buying Shire, but do Pfizer Inc. or Amgen Inc. make greater sense to acquire the rare disease specialist?
(Also see "Takeda Sheds Multilab In Brazil As Strategic Priorities Shift" - Scrip, 5 Apr, 2018.)	Takeda is selling its Multilab Indústria e Comércio de Produtos Farma operation in Brazil, in a reversal of a deal to buy the mid-sized company around six years ago to bolster its position and generic/OTC portfolios in the country.