On November 19, 2021 BridgeBio Pharma, Inc. (Nasdaq: BBIO), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, and Helsinn Group, a fully integrated, global biopharma company with a diversified pipeline of innovative oncology assets and strong track record of commercial execution, reported thart they have entered into a strategic collaboration to co–develop and co-commercialize a potentially first-in-class inhibitor designed to target glutathione peroxidase 4 (GPX4) with the hope of providing an effective new therapy for patients with difficult-to-treat tumors (Press release, Bridge Biotherapeutics, NOV 19, 2021, View Source [SID1234595850]).

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The joint collaboration for BridgeBio’s GPX4 inhibitor was established as part of a new non-exclusive collaboration framework between BridgeBio and Helsinn that allows the companies to propose co-development and co-commercialization opportunities for preclinical precision oncology programs.

Under the terms of the non-exclusive agreement, BridgeBio and Helsinn will have the option to collaborate on preclinical oncology programs that are identified from time to time by either party. The agreement is designed to magnify the ability of both companies to identify small oncology interventions that may have greater potential to help patients in combination with larger investigational therapies. For each program that the parties agree to pursue, they will share global development responsibilities under an agreed cost split. Helsinn will have exclusive manufacturing and commercial rights to the programs under the agreement, with BridgeBio receiving a profit share on U.S. sales and tiered royalties on ex-U.S. sales.

The first program under the framework collaboration agreement that the parties will pursue is GPX4, a potentially first-in-class inhibitor that may be an effective new therapy for certain cancer patients. GPX4 is an enzyme that is often elevated in cancer tissue and associated with a worse prognosis for patients. GPX4 neutralizes toxic free radicals at the lipid membrane, protecting cells from death by ferroptosis. The GPX4 inhibitor is being developed to induce ferroptosis in cancer cells with the potential to impact approximately 500,000 patients in need of a therapeutic option. The safety and efficacy of GPX4 has not yet been established by any health authority world-wide.

"We are excited to expand our collaboration with Helsinn to develop and potentially commercialize our GPX4 program. Our hope is that together we can move even more swiftly to advance this potential precision oncology therapy for cancer patients living with severe unmet medical needs," said BridgeBio’s chairman of oncology, Frank McCormick, Ph.D., F.R.S., D.Sc. (Hon).

Riccardo Braglia, vice chairman and CEO at Helsinn Group, commented: "This non-exclusive pipeline agreement with BridgeBio has the potential to be transformational for Helsinn because BridgeBio’s world class drug discovery platform can augment our innovative oncology pipeline. It also affords Helsinn the opportunity to identify and offer potential programs on which the parties could collaborate. BridgeBio’s deep expertise in drug hunting and early preclinical development combined with Helsinn’s drug development and global commercial platform can facilitate an ongoing cadence of moving novel therapies into clinical development with the potential to meaningfully improve the lives of patients with cancer. We’re delighted to get started with our first program, GPX4, and look forward to updating the market on this and additional programs in due course."

The non-exclusive framework agreement builds on an earlier global collaboration and licensing agreement that BridgeBio and Helsinn Group’s affiliates, Helsinn Healthcare S.A. and Helsinn Therapeutics (U.S.), Inc., entered into in March 2021. Under that agreement, Helsinn Therapeutics is jointly responsible for further development and commercialization activities for infigratinib, a small molecule kinase inhibitor of FGFR, in oncology and all other indications except for skeletal dysplasias (including achondroplasia) in the United States and other regions (excluding China, Hong Kong, and Macau), sharing profits and losses on an equal basis. This includes exclusive commercialization rights for infigratinib in Canada, where Health Canada recently approved TRUSELTIQ (infigratinib) under the Notice of Compliance with Conditions (NOC/c) policy, for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma (CCA) with a FGFR2 fusion or other rearrangement. Helsinn will fund the majority of ongoing and future research and development related to infigratinib in oncology in the foregoing territory. BridgeBio will be eligible for tiered royalties as a percentage of adjusted net sales, and potential payments totaling up to $2.45 billion USD in the aggregate. BridgeBio previously entered a strategic collaboration with LianBio for development and commercialization of infigratinib in oncology indications in China, Hong Kong and Macau.

On November 19, 2021 BioNTech SE (Nasdaq: BNTX, "BioNTech" or "the Company") reported that the U.S. Food and Drug Administration (FDA) granted Fast Track Designation for BNT111, an investigational cancer immunotherapy for the potential treatment of advanced melanoma (Press release, BioNTech, NOV 19, 2021, View Source [SID1234595849]). BNT111 is the lead product candidate from BioNTech’s fully owned FixVac platform that utilizes a fixed combination of mRNA-encoded, tumor-associated antigens aiming to trigger a strong and precise immune response against cancer. The vaccine candidate is currently being investigated in a Phase 2 trial (EudraCT No.: 2020-002195-12; NCT04526899) in patients with anti-PD-1-refractory/relapsed unresectable Stage III or IV melanoma.

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"The Fast Track Designation underlines the potential of our FixVac platform to address current treatment challenges of pre-treated and immune checkpoint blocker experienced melanoma with limited standard of care therapy options left. This is an important step to pave the way for this versatile new treatment approach in a high medical need setting," said Özlem Türeci, M.D., Co-founder and Chief Medical Officer of BioNTech. "With the Fast Track status and support by the FDA, we aim to expedite the further development of the BNT111 program to provide a new therapeutic option for patients with life-threatening, hard-to-treat melanoma."

Fast Track is a process designed to facilitate the development, and expedite the review, of new drugs and vaccines that are intended to treat or prevent serious conditions that have the potential to address an unmet medical need. The FDA’s decision is based on available preclinical and clinical data showing the potential of BNT111 to overcome current limitations in the treatment of inoperable therapy-resistant advanced-stage melanoma. With the Fast Track Designation, the development of BNT111 can benefit from more frequent engagement with the FDA, which will support the collection of appropriate data needed to accelerate BNT111’s development.

The ongoing randomized Phase 2 trial (BNT111-01) in patients with anti-PD1-refractory/relapsed unresectable Stage III or IV melanoma investigates BNT111 in combination with Libtayo (cemiplimab), an anti-PD-1 monoclonal antibody being co-developed by Regeneron and Sanofi. The BNT111-01 trial which is conducted in collaboration with Regeneron is enrolling a total of 180 patients into three treatment arms in the United States, the United Kingdom, Australia, Spain, Germany, Italy and Poland. This trial seeks to support initial data reported from the ongoing Phase 1 Lipo-MERIT monotherapy dose escalation trial (EudraCT No. 2013-001646-33; NCT02410733; DOI: 10.1038/s41586-020-2537-9) that demonstrated a favorable safety profile and anti-tumor responses of BNT111 alone and in combination with immune checkpoint inhibitor therapy in patients with advanced melanoma.

About BNT111
BNT111 is an intravenous therapeutic cancer immunotherapy candidate encoding a fixed set of four cancer-specific antigens optimized for immunogenicity and delivered as RNA-lipoplex formulation. Based on current data from an exploratory interim analysis of the ongoing Phase 1 Lipo-MERIT monotherapy dose escalation trial, published in Nature, BNT111 induces novel antigen-specific anti-tumor immune responses and enhances pre-existing immune responses against the encoded melanoma-associated antigens (NY-ESO-1, MAGE-A3, tyrosinase, and TPTE), which are expressed in more than 90% of cutaneous melanomas. BNT111 is one of four clinical-stage FixVac product candidates within BioNTech’s development pipeline.

BNT111 is not yet authorized by any regulatory authority and the safety and efficacy has not yet been established.

On November 19, 2021, Kezar Life Sciences, Inc. (the "Company") reported that entered into a Sales Agreement (the "Sales Agreement") with Cowen and Company, LLC ("Cowen"), with respect to an at-the-market offering program under which the Company may offer and sell, from time to time at its sole discretion, shares of its common stock, par value $0.001 per share (the "Common Stock"), having aggregate gross proceeds of up to $100.0 million (the "Shares") through Cowen as its sales agent (Filing, 8-K, Kezar Life Sciences, NOV 19, 2021, View Source [SID1234595848]).

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Under the Sales Agreement, the Company will set the parameters for the sale of Shares, including the number of Shares to be issued, the time period during which sales are requested to be made, limitations on the number or dollar value of Shares that may be sold in any one trading day and any minimum price below which sales may not be made. Subject to the terms of the Sales Agreement, Cowen may sell the Shares by any method that is deemed to be an "at the market offering" as defined in Rule 415(a)(4) promulgated under the Securities Act of 1933, as amended (the "Securities Act"), including sales made directly on The Nasdaq Global Select Market or any other trading market for the Common Stock. The Company will pay Cowen a commission equal to three percent (3.0%) of the gross sales proceeds of any Shares sold through Cowen under the Sales Agreement, and has provided Cowen with customary indemnification and contribution rights. The Sales Agreement will terminate upon the earlier of (i) the sale of all Shares subject to the Sales Agreement or (ii) termination of the Sales Agreement in accordance with its terms.

Any Shares to be offered and sold under the Sales Agreement will be issued and sold pursuant to the Company’s Registration Statement on Form S-3 (File No. 333-248752), which was filed with the Securities and Exchange Commission ("SEC") on September 11, 2020 and which became effective on September 23, 2020 (the "Form S-3"). The Company filed a prospectus supplement with the SEC on November 19, 2021 in connection with the offer and sale of the Shares pursuant to the Sales Agreement.

The foregoing description of the Sales Agreement does not purport to be complete and is qualified in its entirety by reference to the full text of the Sales Agreement, a copy of which is furnished as Exhibit 1.1 to this Current Report on Form 8-K (this "Current Report") and is incorporated herein by reference.

Cooley LLP, counsel to the Company, has issued an opinion to the Company, dated November 19, 2021, relating to the validity of the Shares to be issued and sold pursuant to the Sales Agreement, a copy of which is filed as Exhibit 5.1 to this Current Report.

This Current Report shall not constitute an offer to sell or the solicitation of an offer to buy any Shares, nor shall there be any offer, solicitation or sale of the Shares in any state or country in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or country.

On November 19, 2021 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported the successful completion of the cash tender offer, through a subsidiary, Astros Merger Sub, Inc., for all of the outstanding shares of common stock of Acceleron Pharma Inc. (Nasdaq: XLRN), at a purchase price of $180 per share in cash, without interest and less applicable tax withholding. As of the tender offer expiration at 5:00 p.m., Eastern Time, on Nov. 19, 2021, 38,752,614 shares of common stock of Acceleron were validly tendered and not withdrawn from the tender offer, representing approximately 63.3% of the total number of Acceleron’s outstanding shares (Press release, Merck & Co, NOV 19, 2021, View Source [SID1234595847]). All such shares have been accepted for payment in accordance with the terms of the tender offer, and Astros Merger Sub, Inc. expects to promptly pay for such shares.

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Merck intends to complete the acquisition of Acceleron through a merger of Astros Merger Sub, Inc. with and into Acceleron, with Acceleron being the surviving corporation, in which all shares not tendered into the offer will be cancelled and converted into the right to receive cash equal to the $180 offer price per share, without interest and less any applicable tax withholding. After the completion of the merger, Acceleron will become a wholly owned subsidiary of Merck and the common stock of Acceleron will no longer be listed or traded on the Nasdaq Global Market.

On November 16, 2021 Bright Peak Therapeutics, Inc., a biotechnology company developing next-generation cytokine immunotherapies, reported that it has entered into a license agreement with Livzon Mabpharm, Inc. ("Livzon"), a subsidiary company of Livzon Pharmaceutical Group, to use LZM009, Livzon’s proprietary anti-PD-1 monoclonal antibody currently in late-stage clinical trials, to develop novel PD-1 targeted immunocytokines ("PD-1 ICs") (Press release, Livzon Pharmaceutical Group, NOV 19, 2021, View Source [SID1234595846]). The PD-1 ICs will be comprised of optimized cytokine payloads developed by Bright Peak conjugated to LZM009 for the treatment of a variety of cancers. PD-1 ICs are designed to selectively target and activate cytotoxic CD8+ T cells ("CTLs") that express the inhibitory immune checkpoint PD-1 while avoiding the broad activation of other immune cells. Dual targeting of two receptors on the same CTL with a PD-1 inhibitor and a cytokine payload (cis-signaling) offers the added potential for synergistic efficacy.

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Bright Peak is dedicated to creating next-generation immunotherapies that exploit the potent biological activity of cytokines while showing a significantly improved safety profile. Using Bright Peak’s unique chemical protein synthesis and engineering platform, cytokines can be precisely designed to fine-tune receptor binding, optimize efficacy, and simultaneously insert conjugation handles at any desired site in a protein. This allows for rapid conjugation of enhanced cytokines as payloads to commonly used antibodies, creating novel and proprietary "Bright Peak Immunocytokines." One of the many advantages of Bright Peak’s technology is the ‘off-the-shelf’ ability to convert existing therapeutic antibodies into dual-targeting immunocytokines by a simple and rapid chemical process. The platform also readily enables the screening of various cytokine payloads with differential properties to elicit the desired biological effects. Moreover, Bright Peak’s approach allows the use of antibodies ‘as-is,’ avoiding the complex process of generating recombinant antibody-cytokine fusion proteins which involves lengthy protein expression, optimization and cell-line development.

"We are delighted to license Livzon’s anti-PD-1 monoclonal antibody LZM009 to broadly develop PD-1 directed immunocytokines by leveraging our proprietary platform technology," said Fredrik Wiklund, President and Chief Executive Officer of Bright Peak. "PD-1 inhibitors have changed the landscape of cancer therapy in recent years. However, despite the remarkable efficacy observed in a subset of patients treated with PD-1 inhibitors, most patients do not respond. Bright Peak’s PD-1 ICs have the potential to enhance the activity of PD-1 inhibition to bring the promise of immunotherapy to a greater number of patients."

"We are excited to apply the power and versatility of our synthetic protein engineering platform to generate PD-1 ICs by conjugating optimized cytokine payloads to a clinical stage antibody. PD-1 ICs are designed to utilize the concept of cis-signaling cytokines acting on the same cell that is targeted by the anti-PD-1 antibody. As a result, they are more potent and selective and have an increased capacity to induce superior CD8+ T cell responses," said Bertolt Kreft, Ph.D., Chief Scientific Officer of Bright Peak.

"Livzon’s PD-1 molecule has proprietary patents with broad application potential, and we are very happy to enter into an agreement with Bright Peak who possesses an innovative conjugation and protein engineering technology platform to explore and achieve dual-targeting effects of novel molecules to benefit patients with unmet medical needs," said Jianing Liu, Ph.D., Chief Investment Officer and Head of BD of Livzon Pharmaceutical Group. "Livzon Mabpharm is more than happy to support innovative global R&D with inspiring partners leveraging on our existing pipelines and experience in biologics, and we believe this is one step further to demonstrate Livzon MabPharm’s capabilities and readiness for global outreach," said Jiaming Yang, Ph.D., Executive Vice President of Livzon Mabpharm, Inc.

Under the terms of the license agreement, Bright Peak will receive the right to develop, manufacture and commercialize PD-1 ICs on a worldwide basis while Livzon retains certain rights of first negotiation to obtain exclusivity in the greater China territory. Livzon will receive a one-time upfront cash payment from Bright Peak and is eligible to receive additional cash payments upon the achievement of future development and regulatory milestones, as well as royalties in the low-to-mid single digit percentage range on worldwide net sales. Bright Peak will solely control and fund all activities related to development and commercialization on a worldwide basis, subject to Livzon’s right of first negotiation in greater China.

About LZM009
LZM009 is a human IgG4 monoclonal antibody which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1/ PD-Ligand 1 (PD-L1) pathway and reactivates T cells to kill cancer cells. LZM009 has been approved for clinical trials and completed clinical dose exploration trials in both China and the United States. LZM009 is undergoing extensive clinical trials, including pivotal trials in thymic cancer in China, with promising initial safety and efficacy data.