On February 12, 2024 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported that the independent Data Monitoring Committee (DMC) recommended continuation of the pivotal Phase 3 trial (PRESERVE 2), evaluating trilaciclib in combination with gemcitabine and carboplatin for the first line treatment of metastatic triple negative breast cancer (mTNBC), to the final analysis (Press release, G1 Therapeutics, FEB 12, 2024, View Source [SID1234639981]). This final analysis evaluating Overall Survival (OS) is estimated to occur in the third quarter of 2024 and will be conducted on the intent-to-treat (ITT) population. The DMC did not express any concerns regarding safety or recommend any other changes to the study. G1 remains blinded to all data as the early stopping criteria were not met during the interim analysis.

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"We remain confident in the ability of trilaciclib to ultimately achieve the OS primary endpoint based on the robust survival benefit demonstrated in the prior randomized Phase 2 study, which continued to meaningfully increase over time as patients received subsequent therapies, as well as the increased statistical power for the final analysis of this pivotal study," said Jack Bailey, Chief Executive Officer at G1 Therapeutics. "While a positive interim analysis would have enabled us to bring this therapy to patients in need sooner, we look forward to completing the study and potentially making this meaningful new treatment option available to patients with this highly aggressive form of breast cancer as early as next year."

Trilaciclib, an IV-administered transient CDK4/6 inhibitor, is a first-in-class therapy designed to preserve bone marrow and immune system function during cytotoxic therapy to improve patient outcomes. PRESERVE 2 is a global, multi-center, randomized placebo-controlled, line extension pivotal Phase 3 trial of trilaciclib in patients with locally advanced unresectable or metastatic TNBC. Patients meeting eligibility requirements were randomized 1:1 to receive either trilaciclib or placebo administered prior to first-line gemcitabine and carboplatin (GCb). The regimen is given intravenously (IV) on Days 1 and 8 in 21-day cycles. Treatment is administered until disease progression.

About Triple Negative Breast Cancer (TNBC)
Breast cancer is the most commonly diagnosed cancer worldwide, with over 2.3 million new cases each year. According to the American Cancer Society, nearly 300,000 new cases of invasive breast cancer are diagnosed annually in the U.S. Triple negative breast cancer makes up approximately 15-20% of such diagnosed breast cancers. TNBC is cancer that tests negative for estrogen receptors, progesterone receptors, and excess HER2 protein. Because mTNBC cells lack key growth-signaling receptors, patients do not respond well to medications that block estrogen, progesterone, or HER2 receptors. Instead, treating mTNBC typically involves chemotherapy, radiation, and surgery. TNBC is considered to be more aggressive and have a poorer prognosis than other types of breast cancer. In general, survival rates tend to be lower with mTNBC compared to other forms of breast cancer, and mTNBC is also more likely than some other types of breast cancer to return after it has been treated, especially in the first few years after treatment. It also tends to be higher grade than other types of breast cancer.

On February 12, 2024 Gilead Sciences, Inc. (Nasdaq: GILD) and CymaBay Therapeutics, Inc. (Nasdaq: CBAY) reported a definitive agreement under which Gilead will acquire CymaBay for $32.50 per share in cash or a total equity value of $4.3 billion (Press release, CymaBay Therapeutics, FEB 12, 2024, View Source [SID1234639980]). The addition of CymaBay’s investigational lead product candidate, seladelpar for the treatment of primary biliary cholangitis (PBC) including pruritus, complements Gilead’s existing liver portfolio and aligns with its long-standing commitment to bringing transformational medicines to patients.

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"We are looking forward to advancing seladelpar by leveraging Gilead’s long-standing expertise in treating and curing liver diseases," said Daniel O’Day, Chairman and Chief Executive Officer, Gilead Sciences. "Building on the strong research and development work by the CymaBay team to date, we have the potential to address a significant unmet need for people living with PBC and expand on our existing broad range of transformational therapies."

PBC is a rare, chronic, cholestatic liver disease mainly affecting women (1 in 1,000 women over the age of 40 or about 130,000 total people in the U.S.) that impairs liver function and quality of life. The most common early symptoms of PBC are pruritus (itching) and fatigue, which can be debilitating for some patients. Progression of PBC is associated with an increased risk of liver-related mortality.

Seladelpar is an investigational, oral, selective peroxisome proliferator-activated receptor delta (PPARd) agonist, shown to regulate critical metabolic and liver disease pathways. The United States Food and Drug Administration (FDA) has completed its filing review and accepted a New Drug Application for seladelpar and granted priority review with a Prescription Drug User Fee Act target action date of August 14, 2024.

Seladelpar received FDA Breakthrough Therapy Designation for use in the treatment of PBC including pruritus in patients without cirrhosis or with compensated cirrhosis and PRIME status (EMA), as well as Orphan Drug Designation in the U.S. and Europe for the treatment of patients with PBC.

In the pivotal Phase 3 RESPONSE trial, seladelpar achieved statistical significance over placebo across primary composite endpoints of biochemical response (61.7% for patients on seladelpar vs 20.0% for placebo), normalization of alkaline phosphatase at 12 months (25.0% for patients on seladelpar vs 0.0% for placebo) and statistically significant improvement in pruritus at six months among people living with moderate-to-severe itch that was sustained through 12 months.

"Today’s agreement with Gilead is the culmination of years of focus and determination at CymaBay to advance seladelpar and bring new hope to people living with PBC and their families," said Sujal Shah, President, and CEO at CymaBay Therapeutics. "Now that seladelpar has achieved priority review with the FDA, we are excited that Gilead, with its long-standing commitment to patients with liver disease, can apply its regulatory and commercial expertise to bring seladelpar as quickly as possible to people with PBC."

Terms of the Transaction

The transaction was approved by both the Gilead and CymaBay Boards of Directors and is anticipated to close during the first quarter of 2024, subject to regulatory approvals and other customary closing conditions.

Under the terms of the merger agreement entered into in connection with the transaction, a wholly-owned subsidiary of Gilead will promptly commence a tender offer to acquire all of the outstanding shares of CymaBay’s common stock at a price of $32.50 per share in cash, which offer price represents a 27 percent premium to CymaBay’s closing share price on February 9, 2024. Following successful completion of the tender offer, Gilead will acquire all remaining shares not tendered in the offer through a second step merger at the same price as in the tender offer. Upon FDA approval of seladelpar, the proposed transaction is expected to enhance Gilead’s revenue growth, and it is also expected that the transaction will be approximately neutral to earnings per share in 2025 and significantly accretive thereafter.

Consummation of the tender offer is subject to a minimum tender of at least a majority of then-outstanding CymaBay shares, the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act and other customary conditions.

BofA Securities, Inc. and Guggenheim Securities, LLC are acting as financial advisors to Gilead. Centerview Partners LLC and Lazard are acting as financial advisors to CymaBay.

About Seladelpar

Seladelpar, an investigational treatment for people with PBC, is an oral, selective peroxisome proliferator-activated receptor delta (PPARd) agonist shown to regulate critical metabolic and liver disease pathways in indications with high unmet medical need. Preclinical and clinical data support its ability to regulate genes involved in bile acid synthesis, inflammation, fibrosis and lipid metabolism, storage, and transport.

On February 12, 2024 Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX), a clinical stage pharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for rare endocrine diseases and endocrine-related tumors, reported that  the Compensation Committee of Crinetics’ Board of Directors granted non-qualified stock option awards to purchase an aggregate of 73,000 shares of its common stock to nine new non-executive employees under the Crinetics Pharmaceuticals, Inc. 2021 Employment Inducement Incentive Award Plan (the "2021 Inducement Plan") (Press release, Crinetics Pharmaceuticals, FEB 12, 2024, View Source [SID1234639979]). The stock options were granted as inducements material to the employees entering into employment with Crinetics in accordance with Nasdaq Listing Rule 5635(c)(4).

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The 2021 Inducement Plan is used exclusively for the grant of equity awards to individuals who were not previously employees of Crinetics, or following a bona fide period of non-employment, as an inducement material to such individuals’ entering into employment with Crinetics, pursuant to Nasdaq Listing Rule 5635(c)(4).

The options have an exercise price of $39.46 per share, which is equal to the closing price of Crinetics’ common stock on The Nasdaq Global Select Market on February 9, 2024. The shares subject to the stock options will vest over four years, with 25% of the shares vesting on the one-year anniversary of the applicable vesting commencement date and the balance of the shares vesting in a series of 36 successive equal monthly installments thereafter, subject to each employee’s continued employment with Crinetics on such vesting dates. The options are subject to the terms and conditions of the 2021 Inducement Plan and the terms and conditions of a stock option agreement covering the grant.

On February 12, 2024 Cidara Therapeutics, Inc. (Nasdaq: CDTX), a biotechnology company using its proprietary Cloudbreak platform to develop drug-Fc conjugate (DFC) immunotherapies designed to save lives and improve the standard of care for patients facing serious diseases, reported receipt of an $11.14 million milestone payment from Mundipharma following the European approval of REZZAYO (rezafungin acetate), a novel, once-weekly echinocandin antifungal approved for the treatment of invasive candidiasis in adults (Press release, Cidara Therapeutics, FEB 12, 2024, View Source [SID1234639978]).

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This approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use (CHMP) and is based on results from the pivotal ReSTORE Phase III clinical trial, which demonstrated statistical non-inferiority for rezafungin, dosed once weekly, when compared to the standard of care, caspofungin, dosed once daily. The drug was previously approved by the United States Food and Drug Administration (FDA) for the treatment of candidemia and invasive candidiasis in patients with limited or no treatment options.

"The European approval of REZZAYO marks a significant milestone for patients who are in need of new treatment options for invasive candidiasis, and we look forward to seeing Mundipharma bring it to the EU market," said Jeffrey Stein, Ph.D., president and chief executive officer of Cidara. "With the payment we’ve received from this milestone, we remain committed to advancing our Cloudbreak platform to develop targeted immunotherapies for cancer patients."

Cidara is currently advancing its Cloudbreak drug-Fc conjugate (DFC) platform to design targeted immunotherapies that inhibit specific diseases while simultaneously engaging the immune system. Its lead oncology DFC, CBO421, is a potential best-in-class inhibitor of CD73, a validated target highly expressed on tumor cells. An IND is anticipated this year.

On February 12, 2024 Bristol Myers Squibb (NYSE: BMY) and RayzeBio, Inc. (Nasdaq: RYZB) reported the expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, or HSR Act, in connection with Bristol Myers Squibb’s previously reported tender offer to acquire all of the outstanding shares of RayzeBio common stock for a purchase price of $62.50 per share in cash, or approximately $4.1 billion (Press release, Bristol-Myers Squibb, FEB 12, 2024, View Source [SID1234639977]). The expiration of the waiting period occurred at 11:59 p.m. EST on February 9, 2024.

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Expiration of the waiting period under the HSR Act satisfies one of the conditions necessary for the consummation of the transaction, including the tender offer and the merger, which remains subject to the tender of a majority of the outstanding shares of RayzeBio’s common stock, as well as other customary closing conditions. Unless the tender offer is extended, the offer will expire one minute after 11:59 p.m. New York City time, on February 22, 2024.