In a BIO Digital session on “The Convergence of Health and Tech: Personalizing Medicine Beyond the Imaginable,” panelist Ray Deshaies, Amgen Inc.’s senior vice president of global research, said he was excited for the future of drug research, noting that there is an evolving trend away from the development of monospecific drugs designed to exert their effect on just one specific target. The early stage product pipelines of biopharma companies are now adding bi- or multispecific drug candidates that exert an influence on several mechanisms in the cell, either simultaneously or sequentially. He noted that this is a sea change that is beginning to sweep over the industry. Biopharma companies are now beginning to uncover ways to counteract unwanted disease-causing proteins that have previously been difficult to block using a single small-molecule drug approach.

Product development

The FDA sent a complete response letter to Allergan plc, an Abbvie Inc. company, and Molecular Partners AG regarding the BLA for abicipar pegol, their VEGF-A inhibitor-Darpin therapy for patients with wet age-related macular degeneration. In the letter, the FDA noted the rate of intraocular inflammation occurring after administering abicipar pegol 2 mg/0.05 mL results in an unfavorable benefit-risk ratio. Abbvie said it will meet with the FDA to discuss the comments and determine next steps.

Chiasma Inc. secured U.S. approval for Mycapssa, the first oral formulation of the acromegaly medicine octreotide to get a regulatory green light. Octreotide has until now only been available by injection. The drug was approved for long-term maintenance treatment in acromegaly patients who have responded to and tolerated treatment with octreotide or lanreotide, both somatostatin analogues.

Xpovio (selinexor), an oral selective inhibitor of nuclear transport from Karyopharm Therapeutics Inc., received FDA approval for treating adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. The drug will be available immediately in the U.S., the company said, and, due to COVID-19 restrictions, the launch will be a virtual one.

A second attempt by Nabriva Therapeutics plc to win U.S. approval for the antibiotic Contepo (fosfomycin) has been undone by COVID-19. Manufacturing issues stymied the original NDA. This time, restrictions of FDA staff travel to Europe sunk the venture, leading to a new complete response letter (CRL) for the candidate as a potential treatment of complicated urinary tract infections, including acute pyelonephritis. The company warned of the potential for the CRL in May. The agency did not request any new clinical data, nor did it raise any other concerns about the safety or efficacy of Contepo in the CRL.

The FDA approved Zogenix Inc.’s Fintepla (fenfluramine), an oral treatment for patients ages 2 and older with seizures associated with Dravet syndrome, a rare, pediatric-onset form of epilepsy.

COVID-19 developments

Two months after the launch, the World Health Organization (WHO) has laid out the spending plans for its push to accelerate development and production of COVID-19 vaccines, therapeutics and diagnostics.

The consolidated investment case calls for $31.3 billion over the next 12 months, of which $3.4 billion has been contributed to date. The money will accelerate development and fund delivery of 500 million diagnostic tests and 245 million courses of therapies to poorer countries by mid-2021, with 2 billion doses of vaccine, of which 1 billion will go the poorer countries to be delivered by the end of 2021. The investment is significant, but WHO said the total cost is less than a 10th of the $375 billion the global economy is losing every month due to the pandemic.

A new U.K. trial evaluating drugs for hospitalized patients in the early stages of COVID-19 has elected to test Evelo Biosciences Inc.'s anti-inflammatory monoclonal microbial, EDP-1815, after an earlier trial found it led to favorable anti-inflammatory activity in psoriasis patients. Interim data from the trial, called TACTIC-E, are anticipated during the fourth quarter. If results of the phase II/III study are positive, Evelo said its team will engage with regulators to determine if the data support registration. Glenmark Pharmaceuticals Ltd. has been granted manufacturing and marketing approval for the launch of its antiviral drug, favipiravir, for the treatment of mild to moderate COVID-19, a move it deems a “landmark development for COVID-19 patients in India.” Glenmark filed the product for use in clinical trials with the Drug Controller General of India (DCGI) and became the first pharmaceutical company in India to receive approval to conduct a phase III study in patients with mild to moderate disease caused by the SARS-CoV-2 virus.

Applied Biology Inc. said that a team of scientists, while studying the genetics of the androgen receptor in male pattern baldness, discovered a possible breakthrough treatment for COVID-19. Immunoprecise Antibodies Ltd. and Litevax BV will collaborate on a preclinical study to analyze the immunogenicity, safety and potency of Immunoprecise's SARS-CoV-2 vaccine candidates. Orgenesis Inc. entered a preliminary, nonbinding term sheet with Leidos Holdings Inc. to develop Orgenesis’ ranpirnase to treat severe acute respiratory syndrome associated with SARS-CoV-2. Ranpirnase catalyzes the degradation of RNA and mediates several biological activities, including regulation of cell proliferation, maturation, differentiation and cell death. Moderna Inc. and Catalent Inc. will collaborate on large-scale, commercial fill-finish manufacturing of Moderna’s mRNA-based COVID-19 vaccine candidate, mRNA-1273, at Catalent’s biologics facility in Bloomington, Ind. Catalent will provide vial filling, packaging capacity and additional staffing required for round-the-clock manufacturing operations to produce an initial 100 million doses of the vaccine candidate intended to supply the U.S. market starting in the third quarter of 2020. Palatin Technologies Inc. is developing melanocortin 1 receptor agonist PL-8177 as a treatment for patients with COVID-19 after a preclinical test in multiple inflammatory disease models and a lung injury model showed it reduced inflammation, protected lung tissue and reduced lung fibrosis. Schrödinger Inc. said it is expanding its work to discover new antiviral therapies for COVID-19. The company is leading the computational design work in an alliance of major biopharma companies collaborating on the COVID-19 initiative, including Takeda Pharmaceutical Co. Ltd., Novartis AG, Gilead Sciences Inc. and Wuxi Apptec.

Deals of the week

CSL Behring has licensed global rights to Uniqure NV's late-stage hemophilia B gene therapy candidate, AMT-061, for $450 million up front, plus up to $1.6 billion in potential milestone payments and royalties. Gilead Sciences Inc. has acquired a 49.9% equity interest in privately held Pionyr Immunotherapeutics Inc., which could receive up to $1.15 billion in potential future milestone payments in the deal. Pionyr’s Myeloid Tuning technology aims to rebalance the tumor microenvironment (TME) and is designed to treat patients who don’t benefit from checkpoint inhibitor therapies. A significant volume of the TME is composed of myeloid cells, but in some cases they have been hijacked by the cancer. Some help the tumor grow while others stimulate the immune system.

La Jolla Pharmaceutical Co. and Tetraphase Pharmaceuticals Inc. signed a definitive merger agreement. Under the terms, La Jolla would acquire Tetraphase, through a tender offer, for $43 million in up-front cash plus potential future cash payments of up to $16 million pursuant to contingent value rights.

Lantheus Holdings Inc. completed its merger with Progenics Pharmaceuticals Inc. Sarepta Therapeutics Inc. and Codiak Biosciences Inc. entered a global research and option agreement to design and develop engineered exosome therapeutics for delivering gene therapy, gene editing and RNA technologies to neuromuscular diseases. The two-year agreement includes up to five neuromuscular targets. Translate Bio Inc. will receive $300 million up front, another $125 million in equity investment and up to $1.9 billion in milestones under a major expansion of an existing agreement with Sanofi SA to develop mRNA-based vaccines for infectious disease. Translate Bio will also receive tiered royalties on product sales. Sosei Heptares has attracted a third pharma partner to its G protein-coupled receptor discovery platform, signing a potential $1 billion-plus deal with Abbvie Inc. in inflammatory and autoimmune diseases. Sosei Heptares is getting $32 million in up-front and near-term milestones for all preclinical research, plus potential option, development and commercial milestones totaling $377 million. Vistagen Therapeutics Inc. and Everinsight Therapeutics Inc. entered a licensing and collaboration agreement for the clinical development and commercialization of PH-94B, Vistagen's rapid-onset neurosteroid drug candidate for multiple anxiety-related disorders, in greater China and other Asia markets. Yumanity Therapeutics Inc. said that Merck & Co. Inc. is licensing exclusive rights to programs addressing amyotrophic lateral sclerosis and a rare type of dementia in a deal with up to $500 million in potential milestone payments. The collaboration also includes an up-front payment, money toward a series C financing and potential royalties on net sales of the licensed programs.

Financial transactions

Public offerings: Companies are having no difficulty raising capital, with a number of follow-on deals completed last week including: Actinium Pharmaceuticals Inc., raising gross proceeds of approximately $25 million; Aveo Oncology Inc. raised gross proceeds of $51.1 million; Catalyst Biosciences Inc. raised gross proceeds of approximately $30 million; Castle Biosciences Inc. raised gross proceeds of $74 million. Editas Medicine Inc. raised gross proceeds of approximately $187.5 million; Leap Therapeutics Inc. generated gross proceeds of approximately $51 million; Magenta Therapeutics Inc. is looking to raise gross proceeds of $60 million, excluding any exercise of the underwriters’ option to purchase additional shares; Nantkwest Inc. expects to raise gross proceeds of $80.1 million from a public offering; Soleno Therapeutics Inc. priced its offering for expected gross proceeds of approximately $50 million.

The demand for biopharma IPOs was also strong: Akouos Inc. plans to raise $213 million from its offering; Forma Therapeutics Holdings Inc. closed its IPO that raised gross proceeds of approximately $319.3 million; Fusion Pharmaceuticals Inc. plans to raise up to $188 million; Greenwich Lifesciences Inc. plans to raise up to $21 million; Inmed Pharmaceuticals Inc. plans to raise up to $12 million; Iteos Therapeutics Inc. plans to raise up to $100 million; Nkarta Inc. plans to raise up to $100 million; Polypid looking to raise $50 million; Poseida Therapeutics Inc. filed to raise up to $115 million; Relay Therapeutics Inc. filed to raise up to $200 million; and, Repare Therapeutics Inc. closed its upsized IPO for gross proceeds of $253 million.

Venture funding: Biogeneration Ventures raised €105 million (US$118.7 million) for its fourth fund. Epidarex Capital announced the closure of its £102.1 million (US$126.3 million) third fund, which will invest in very early stage biomedical and med-tech spinouts from high-class but “under-ventured” universities in regions of the country where venture money is in short supply. The fund is cornerstoned by £50 million from the British Business Bank, the government economic development bank, through its Enterprise Capital Fund program, which backs the formation of tech and science startups.

Artiva Biotherapeutics Inc. has secured $78 million in series A financing to support its development of off-the-shelf universal NK cells for use in combination with monoclonal antibody therapy and tumor-targeting CAR-NK cell therapies. Asclepix Therapeutics Inc. closed a $35 million series A financing. Cyclica Inc. closed a CA$23 million (US$16.9 million) series B financing. Evergreen Theragnostics Inc. raised $19 million in a series A financing round. Poseida Therapeutics Inc. has closed on a $110 million series D to continue its CAR T-cell therapy programs. Cell and gene engineering company Sana Biotechnology Inc. raised $700 million in a first-round financing.

Regulatory news

The FDA reported it has launched Project Patient Voice (PPV), created by the agency's Oncology Center of Excellence. The PPV website provides publicly available information describing patient-reported symptoms from cancer trials for marketed treatments. While those data have historically been analyzed by the FDA during the drug approval process, they are rarely included in product labeling and, therefore, are largely inaccessible to the public. The data can provide additional, complementary information for health care professionals, specifically when discussing the potential side effects of a cancer treatment. In the first phase of the pilot website, only one trial will be included while the FDA seeks public feedback on how the information is presented. It will use that feedback to consider improvements to the website in order to make the information as user-friendly as possible.

The FDA has finalized its guidances on the clinical development of drugs to treat community-acquired bacterial pneumonia (CAPB) and hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP). They discuss the overall development program and clinical trial designs for drugs to support an indication of CAPB or HABP/VABP.

Word on the Street: Industry responses to the issues of the week

“In terms of launching in the virtual environment, given the pandemic started in Q1, we've known for quite some time that a virtual launch would be necessary, and we've been preparing accordingly. All of our field teams have been provided additional tools to virtually engage with customers. We rapidly launched multiple digital tools to facilitate continued sales force engagement with customers, and the field team has been trained on how to utilize these tools with the appropriate promotional pieces in DLBCL.”
Ian Karp, Karyopharm Therapeutics Inc.’s vice president of investor and public relations, speaking on conference call to investors about the FDA approval of Xpovio (selinexor), an oral selective inhibitor of nuclear transport for treating adults with relapsed or refractory diffuse large B-cell lymphoma

"While these agents have demonstrated efficacy in a proportion of cancer patients, there clearly is room for improvement to lift the tail of the curve."
Michele Teng, associate professor at the QIMR Berghofer Medical Research Institute, told the audience at the clinical trials plenary session of the American Association for Cancer Research Virtual Annual Meeting II, where researchers presented data from a pair of immunotherapies looking to build on the success targeting PD-(L)1

"In the tissue-agnostic approvals to date, we believe that based on the biology and clinical results, that we can infer clinical effects across a wide variety of tumors. The chance of each rare biomarker-positive tumor responding will be higher than the chance that a specific tumor type will be inherently resistant."
Steven Lemery, acting director of the division of oncology at the FDA, speaking at a session of the American Association for Cancer Research Virtual Annual Meeting II, noting that if a resistance was found in a certain tumor type, the label could be modified to note the exception

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