Passing the 21st Century Cures Act during the lame duck session of Congress following the elections is a high priority, Senate Majority Leader Mitch McConnell (R-Ky.) and House Speaker Paul Ryan (R-Wis.) each said Thursday. The House passed a version of the bill (H.R. 6) in July 2015, but the Senate has not passed companion legislation (see BioCentury, April 18).
Briefing reporters, McConnell said he has two priorities for the lame duck session: "funding the government and the 21st Century Cures bill, which I think could end up being the most significant piece of legislation we pass in the whole Congress." McConnell noted that President Obama favors the bill because it would fund the Precision Medicine Initiative and Vice President Biden supports it because it would fund the Cancer Moonshot Initiative.
McConnell added that he favors its enactment because of his interest in regenerative medicine. He is pushing to incorporate the Reliable and Effective Growth for Regenerative Health Options that Improve Wellness (REGROW) Act (S. 2689) into the Senate version of 21st Century Cures legislation. REGROW would create a pathway for FDA to conditionally approve cellular therapies based on "preliminary clinical evidence of safety, and a reasonable expectation of effectiveness, without initiation" of Phase III trials.
Ryan told reporters the 21st Century Cures Act is one of several bills already passed by the House that could also be passed by the Senate in the lame duck session. In a statement Wednesday, Senate Health, Education, Labor and Pensions Committee Chairman Lamar Alexander (R-Tenn.) and the committee's ranking Democrat Patty Murray (D-Wash.) said they are continuing to work on a Senate version of the bill, and are "committed to getting a result this year that will lead to lifesaving medical breakthroughs and advance President Obama's Precision Medicine Initiative and Vice President Biden's Cancer Moonshot."
Despite the expressions of support, enactment in the current session of Congress is far from certain. Since the House passed H.R. 6, its budget offsets were reallocated by Congress for other purposes.
In two deals with Arrowhead Pharmaceuticals Inc. (NASDAQ:ARWR), Amgen Inc. (NASDAQ:AMGN) obtained exclusive, worldwide rights to cardiovascular program ARC-LPA and gained an exclusive option to license a second RNAi therapy against an undisclosed cardiovascular target Amgen has selected.
Arrowhead will receive a combined $35 million up front plus $21.5 million in an equity investment through Amgen's purchase of 3 million shares at $7.16. Arrowhead is also eligible for $617 million in option exercise fees and milestones, plus low double-digit royalties on sales of ARC-LPA and single-digit royalties for sales on the therapy for the undisclosed target.
ARC-LPA is a preclinical RNAi-based therapeutic that is designed to reduce the production of apolipoprotein A (APOE). Amgen spokesperson Kristen Davis declined to comment on when the company expects to start clinical testing of the compound. Arrowhead said it is the company's first candidate to use Arrowhead's subcutaneous delivery construct. The therapy in the companies' other deal will also use the subcutaneous delivery technology.
Arrowhead added $0.26 to $7.30 on Thursday. Amgen slipped $4.26 to $165.45.
Hanmi Pharmaceutical Co. Ltd. (KOSDAQ:128940) granted the Genentech Inc. unit of Roche (SIX:ROG; OTCQX:RHHBY) exclusive, worldwide rights, excluding South Korea, to develop and commercialize oncology candidate HM95573, a pan-RAF inhibitor that is in Phase I testing.
Hamni will receive $80 million up front and is eligible for up to $830 million in milestones, plus double-digit royalties.
HM95573 was Hanmi's most advanced unpartnered clinical new chemical entity (NCE) program (see BioCentury, Feb. 8).
Hanmi gained W6,000 to W620,000 on Thursday. The news was released after market close in Korea.
Tesaro Inc. (NASDAQ:TSRO) granted Zai Lab Ltd. (Shanghai, China) exclusive rights to develop and commercialize ovarian cancer candidate niraparib (MK-4827) in Greater China, including Hong Kong and Macau. Zai also granted Tesaro an option to license ex-Chinese rights to two of Zai's discovery stage immuno-oncology programs.
Tesaro will receive $15 million up front and is eligible for undisclosed development and commercialization milestones, plus tiered royalties. Tesaro also retained an option to co-promote niraparib in Greater China.
Next quarter, Tesaro expects to complete submission of a rolling NDA to FDA for niraparib, an oral PARP inhibitor, to treat recurrent, platinum-sensitive ovarian, fallopian tube or primary peritoneal cancer.
Last year, Tesaro granted Jiangsu Hengrui Medicine Co. Ltd. (Shanghai:600276) exclusive Chinese rights to rolapitant (SCH 619734), which is now approved in the U.S. to treat chemotherapy-induced nausea and vomiting (CINV) (see BioCentury Extra, July 30, 2015).
Tesaro lost $3.84 to $100.58 on Thursday.
Celgene Corp. (NASDAQ:CELG) exercised an option giving it ex-U.S. rights to ABX-1431 from Abide Therapeutics Inc. (San Diego, Calif.). The small molecule inhibitor of monoacylglycerol lipase (MAGL) is in Phase I testing for neurological diseases.
The option exercise triggers a $20 million fee to Abide from Celgene, which will be responsible for development costs for all indications in Phase II and beyond. Abide, which retains U.S. rights, plans to conduct additional Phase Ib studies in neuromyelitis optica and movement disorders.
MAGL modulates levels of 2-arachidonoylglycerol (2-AG), which Abide said may regulate neurotransmitter balance and inflammation.
Celgene gained the option under a 2014 deal. That agreement also gave Celgene a second option to license ex-U.S. rights to the next Abide compound targeting serine hydrolases that reaches the clinic for inflammation and immunological disorders, as well as an exclusive option to acquire Abide for undisclosed terms. Celgene still holds both outstanding options (see Biocentury, March 10, 2014).
Catabasis Pharmaceuticals Inc. (NASDAQ:CATB) gained $1.77 (40%) to $6.25 Thursday after it partnered with Sarepta Therapeutics Inc. (NASDAQ:SRPT) to study a combination treatment for Duchenne muscular dystrophy.
In a mouse model of DMD, the partners will evaluate Catabasis' edasalonexent (CAT-1004), a conjugate of salicylate and docosahexaenoic acid (DHA) that inhibits NF-kappa B, in combination with Sarepta's exon skipping technology. Catabasis is conducting a Phase II trial of edasalonexent to treat DMD.
Last week, FDA approved Sarepta's Exondys 51 eteplirsen, a phosphorodiamidate morpholino oligomer (PMO) that induces skipping of exon 51 dystrophin mRNA (see BioCentury Extra, Sept. 19).
bluebird bio Inc. (NASDAQ:BLUE) and Medigene AG (Xetra:MDG1) partnered to develop T cell receptor immunotherapies against four undisclosed targets to treat cancer.
The companies intend to collaborate on preclinical development. Medigene will be responsible for producing TCRs and bluebird will be responsible for clinical development and commercialization, and will have exclusive rights to any candidates produced in the partnership.
Medigene is to receive $15 million up front and is eligible for more than $1 billion in milestones, plus tiered royalties. bluebird also will provide Medigene with R&D funding.
Medigene gained EUR 1.11 (16%) to EUR 8.07 on Thursday. bluebird shed $2.70 to $66.41.
Prime Therapeutics LLC (Eagan, Minn.) said outcomes-based contracts with drug manufacturers should be considered to encourage patient adherence and cost-effectiveness of treatment plans for chronic diseases. The comments came after a Prime study showed that 44% of rheumatoid arthritis patients receiving Xeljanz tofacitinib discontinued the treatment after one year.
Pfizer Inc. (NYSE:PFE) markets Xeljanz, an oral pan-Janus kinase (JAK) inhibitor.
Prime called the discontinuation rate "concerning" and said that one in 10 RA patients used Xeljanz as a first-line therapy, without using a disease-modifying anti-rheumatic drug (DMARD) in the previous year. Xeljanz is approved in the U.S. as a second-line therapy for RA.
The PBM said a lack of long-term efficacy data for Xeljanz and a wholesale acquisition cost (WAC) of more than $42,000 per year suggest a need to understand the drug's "real world" utilization.
Prime said it will present its Xeljanz analysis next week at the Academy of Managed Care Pharmacy Nexus.
Novo Nordisk A/S (CSE:NVO; NYSE:NVO) said it plans to reduce its workforce by about 1,000 employees as part of an effort to reduce operating costs.
The company currently has 42,300 positions globally, and expects about half the cuts to occur in Denmark. The reductions are to affect R&D units, headquarters staff and the company's global commercial organization.
Spokesperson Ken Inchausti said it was "too early to speculate" on which research units and R&D areas would be affected.
Novo has faced headwinds in the diabetes market due to increased competition and pricing pressure. In August, President and CEO Lars Sorensen said the U.S. diabetes environment is "becoming increasingly challenging and contract negotiations for 2017 have reflected an intensified price competition" (see BioCentury Extra, Sept. 1).
Sorensen is retiring Jan. 1, 2017.
In a paper published online Thursday in Cell, University of California San Francisco researchers showed T cells engineered to express a synthetic Notch (synNotch) receptor could be programmed to produce a diverse array of therapeutic agents in the presence of disease-specific molecular cues. Cell Design Labs Inc. (San Francisco, Calif.) has licensed the technology from UCSF.
SynNotch receptors are altered versions of Notch cell surface proteins composed of modular, custom-selected extracellular sensing and intracellular response domains. In a cell expressing synNotch receptors, extracellular domain binding to a target ligand triggers expression of a pre-specified gene or set of genes. In a previous Cell study from the same laboratory, synNotch receptors were used to induce T cell expression of chimeric antigen receptors (CARs) only in the presence of specific tumor antigens (see BioCentury Extra, January 29).
Wendell Lim, a UCSF professor and co-founder of Cell Design Labs, told BioCentury that synNotch "can be many different tools, depending on how it's deployed."
In Thursday's study, Lim's team engineered T cells to express different versions of the synNotch receptor that induced secretion of therapeutic proteins -- such as an apoptosis inducer, individual cytokines or pairs of them, checkpoint inhibitor antibodies or other immune modulators -- when cells were exposed to specific ligands, such as CD19 or green fluorescent protein (GFP). In a bilateral subcutaneous xenograft mouse model of chronic myelogenous leukemia (CML), in which tumors on one flank expessed the synNotch ligand GFP while tumors on the opposite flank did not, T cells programmed to produce Blincyto blinatumomab upon synNotch activation only induced regression of GFP-positive tumors.
Amgen Inc. (NASDAQ:AMGN) markets Blincyto, a bispecific T cell engager (BiTE) against CD19, to treat acute lymphoblastic leukemia (ALL).
Lim noted synNotch T cells could enable therapeutic use of agents that are toxic when delivered systemically, such as interleukin-12 (IL-12), by producing them locally at disease sites. He added that while the technology could be applied in many diseases, it would most likely be used to enhance T cell functions in oncology.
Cell Design CEO Brian Atwood told BioCentury the company plans to use the technology to target two undisclosed cancer indications, with clinical trials starting in 2018. He said Cell Design is also seeking partnerships for the technology.
Alnylam Pharmaceuticals Inc. (NASDAQ:ALNY) said it will discontinue development of ALN-AAT for alpha-1 antitrypsin (AAT; A1AT; SERPINA1) deficiency-associated liver disease due to a low incidence of elevated liver enzymes observed in a Phase I/II trial. The biotech intends to select a follow-on candidate, for which it plans to submit a CTA next year.
In a presentation at the Oligonucleotide Therapeutics Society meeting in Montreal, Alnylam's data showed that ALN-AAT led to "dose-dependent, and durable knockdown of serum AAT." The company said a single dose of ALN-AAT led to three instances of asymptomatic, transient elevations of liver enzymes among 15 healthy volunteers.
ALN-AAT is a short interfering RNA (siRNA) targeting AAT conjugated to GalNAc ligand. Alnylam said it will aim to optimize the tolerability profile of the follow-on molecule, which will be named ALN-AAT02 and will target a different sequence.
The Genzyme Corp. unit of Sanofi (Euronext:SAN; NYSE:SNY) has rights outside of North America and Western Europe to some programs in Alnylam's genetic medicines pipeline, including ALN-AAT and ALN-AAT02 (see BioCentury Extra, Jan. 13, 2014).
Alnylam sank $6.73 to $69.94 on Thursday.
ReadCoor Inc. (Boston, Mass.) debuted with $23 million in a series A round to develop and commercialize fluorescent in situ sequencing (FISSEQ) technology from the Wyss Institute for Biologically Inspired Engineering at Harvard University.
Decheng Capital led the round. Lilly Asia Ventures, Vivo Capital and Hansjoerg Wyss also participated.
FISSEQ is a high throughput technology that enables simultaneous sequencing and 3-D visualization of thousands of RNAs within whole cells and tissues for in situ analysis of gene expression.
The FISSEQ platform was incubated within the Wyss Institute. ReadCoor said it will begin providing sequencing services to academia and industry "almost immediately."
Decheng's Victor Tong and Vivo's Yuh-geng Tsay will join ReadCoor's board.
Diagnostics company Fulgent Genetics Inc. (NASDAQ:FLGT) gained $0.18 to $9.18 in its first day of trading Thursday after raising $37.8 million through the sale of 4.2 million shares at $9 in an IPO underwritten by Credit Suisse, Piper Jaffray, Raymond James and BTIG. The offering valued the company at $153.4 million.
On Wednesday, Fulgent said it hoped to sell 4.2 million shares at $9-$11. In its initial filing earlier this month, it proposed to raise up to $50 million.
Fulgent offers genetic tests for more than 7,500 genetic conditions, including cancers, cardiovascular diseases and neurological disorders.
President Barack Obama signed into law H.R. 5325, a continuing appropriations bill that includes $1.1 billion in funds to address the Zika virus. The law will fund the federal government through Dec. 9.
The legislation grants $394 million to the CDC and $152 million to NIH's National Institute of Allergy and Infectious Diseases (NIAID). It also appropriates $387 million for a Public Health and Social Services Emergency Fund "to prevent, prepare for, and respond to Zika virus," both domestically and internationally.
The U.S. House of Representatives passed an amended version of the Advancing Hope Act (S. 1878) that would extend the Rare Pediatric Disease Priority Review Voucher program until YE16. The U.S. Senate passed the bill unanimously last week. The voucher program is scheduled to sunset Oct. 1 (see BioCentury Extra, Sept. 23).
On Wednesday, U.S. Senate Minority Leader Harry Reid (D-Nev.) derailed an effort to enact the Trickett Wendler Right to Try Act of 2016 (S. 2912) by unanimous consent.
The bill's sponsor, Sen. Ron Johnson (R-Wis.), had sought to bypass a committee vote. Reid said he objected because "major players in this haven't had an opportunity to tell us what's wrong with this bill."
Similar legislation is pending in the House, but it is unlikely that either bill will be enacted in the current session of Congress.