On November 30, 2022 Xspray Pharma (Nasdaq Stockholm: Xspray) reported the company received a decision from the US Food and Drug Administration (FDA) granting drug candidate XS004 (dasatinib) Orphan Drug Designation (ODD) for the treatment of acute lymphoblastic leukemia (ALL) (Press release, Xspray, NOV 30, 2022, View Source [SID1234649577]).

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The FDA decision is based on the potential that XS004 may be clinically superior to other drugs already approved for the same indication. Xspray Pharma’s product candidate may provide a major contribution to patient treatment due to the gastric pH-resistant qualities of the formulation and the significant frequency of concomitant use of acid-reducing agents in the ALL population.

"We are pleased that our product candidate XS004 has now been granted orphan drug designation for ALL. It is the second indication where XS004 has been granted this status, further validating our technology and the unmet medical need that Xspray Pharma can address. This strengthens us in our objective to work with improved oncology pharmaceuticals that can give cancer patients a better quality of life," says Per Andersson, CEO of Xspray Pharma.

In June of this year, the FDA granted orphan drug designation status for XS004 (dasatinib) for the treatment of chronic myeloid leukemia (CML). XS004 is Xspray Pharma’s first product candidate currently undergoing FDA review for market approval. The FDA grants orphan drug designation status to potential new drug candidates intended for the treatment, diagnosis, or prevention of rare diseases or disorders that affect fewer than 200,000 people in the United States.

"It is very gratifying that the FDA has recognized the potential for improvement in XS004 as a significant improvement in patients’ quality of life. Xspray will attend the annual international hematology congress organized by the American Society of Hematology (ASH) (Free ASH Whitepaper) this year and will present two scientific posters that may be relevant to the treatment of patients with ALL and CML" says Thomas Walz, CMO of Xspray Pharma.

Acute lymphocytic leukemia – ALL
ALL is an acute form of cancer caused by rapid growth of immature lymphocytes (lymphoblasts) in the bone marrow due to various genetic changes. In 2022, it was estimated that 6,660 people in the United States would be diagnosed with ALL and it is estimated that approximately 100,000 people in the United States have this diagnosis.

On November 30, 2022 Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, reported a clinical trial collaboration and supply agreement (CTCSA) with Pierre Fabre for the BRAF inhibitor encorafenib (BRAFTOVI) within key international territories (Press release, Erasca, NOV 30, 2022, View Source [SID1234639374]).

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This agreement will support a clinical proof-of-concept trial evaluating ERAS-007, an oral ERK1/2 inhibitor, in combination with encorafenib and the anti-EGFR antibody cetuximab for the treatment of patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC). This combination is being investigated as part of the ongoing Phase 1b/2 HERKULES-3 master protocol in patients with gastrointestinal (GI) malignancies. Erasca will sponsor the trial, and Pierre Fabre will supply encorafenib in the Pierre Fabre territories which include Europe and Asia Pacific (excluding Japan and South Korea).

"We are excited to work with Pierre Fabre, a leader in precision oncology, on an international collaboration to explore ERAS-007 in combination with encorafenib and cetuximab in BRAF mCRC," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "This partnership complements our existing CTCSA with Pfizer for encorafenib within the United States and other markets. Resistance mechanisms, particularly through MAPK reactivation, limit long-term benefit with current standard of care BRAF-targeted treatments. By blocking RAS/MAPK pathway signaling at the most distal node, ERK1/2, ERAS-007 can potentially prevent pathway reactivation."

Worldwide, approximately 1.8 million cases of CRC are diagnosed annually, with BRAF V600E mutations occurring in approximately 10% of these patients. Encorafenib in combination with cetuximab was approved by the FDA in April 2020 for previously treated patients with BRAF V600E-mutant mCRC. While the combination demonstrated improved overall survival over chemotherapy, only 20% of patients experienced an objective response, with a progression-free survival of approximately four months. Emergence of resistance remains a major therapeutic barrier to long-term clinical benefit. Erasca is exploring whether ERK inhibition with ERAS-007 in combination with encorafenib plus cetuximab can reduce the emergence of resistance and further improve treatment benefit for patients with BRAF V600E-mutant mCRC.

About ERAS-007
ERAS-007 is a potential best-in-class ERK1/2 inhibitor being investigated alone or in combination with different inhibitors targeting upstream nodes of the MAPK pathway as part of Erasca’s MAPKlamp strategy. The extracellular signal-regulated kinases (ERK), ERK1 and ERK2, belong to a family of serine-threonine kinases that regulate cellular signaling and comprise the terminal node of the RAS/MAPK pathway. ERAS-007 is being investigated across the series of HERKULES clinical trials that span multiple tumor types and includes both monotherapy and combinations with approved and investigational agents, such as RTK, SHP2, RAS, RAF, and/or cell cycle inhibitors. HERKULES-1 is a Phase 1b/2 clinical trial for ERAS-007 as a single agent and in combination with the SHP2 inhibitor ERAS-601 (together, Erasca’s first MAPKlamp) in advanced solid tumors. HERKULES-2 is a Phase 1b/2 master protocol clinical trial for ERAS-007 in combination with various agents in patients with non-small cell lung cancer (NSCLC). HERKULES-3 is a Phase 1b/2 master protocol clinical trial for ERAS-007 in combination with various agents in patients with GI cancers.

On November 30, 2022, BridgeBio Pharma, Inc. ("BridgeBio" or the "Company") entered into a Second Amendment to Loan and Security Agreement (the "Second Amendment"), by and among (i) U.S. Bank Trust Company, National Association, as successor to U.S. Bank National Association, in its capacity as administrative agent (in such capacity, the "Administrative Agent") and collateral agent (in such capacity, the "Collateral Agent"), (ii) the certain lenders party thereto (the "Lenders"), (iii) the Company, as a borrower, and (iv) certain subsidiaries of the Company, as guarantors (the "Guarantors"), pursuant to which the parties thereto agreed to amend the Loan and Security Agreement, dated as of November 17, 2021, as amended by the First Amendment to Loan and Security Agreement, dated as of May 12, 2022 (the "Existing Loan Agreement", and amended by the Second Amendment, the "Amended Loan Agreement"), by and among the Company, Guarantors, Lenders, the Administrative Agent and the Collateral Agent (Filing, BridgeBio, NOV 30, 2022, View Source [SID1234624855]).

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Pursuant to the terms and conditions of the Second Amendment, the parties thereto agreed to, among other things: (1) acknowledge that the Company’s prior prepayment made with certain cash proceeds received in connection with that certain License, Development and Commercialization Agreement, dated as of May 11, 2022, by and among Navire Pharma, Inc., the Company and Bristol-Myers Squibb Company satisfied the mandatory prepayment requirement under the Amended Loan Agreement, on the terms and conditions specified in the Amended Loan Agreement, (2) permit certain budgeted expenses to be excluded from the definition of cash proceeds subject to Borrower’s mandatory prepayment obligations, on the terms and conditions specified in the Amended Loan Agreement, (3) remove certain threshold amounts applicable to certain prepayment events and (4) terminate the Lenders’ tranche 2 commitments. The Company retains the ability to undertake certain royalty financing transactions that do not exceed ten percent (10%) of the net sales in respect of a product, and royalty financing transactions relating to Acoramidis remain exempt from prepayment, subject to the terms and conditions of the Amended Loan Agreement.

Other terms of the Amended Loan Agreement remain generally identical to those under the Existing Loan Agreement.

The above description of the material terms of the Second Amendment does not purport to be complete and is qualified in its entirety by reference to the full text of the Second Amendment, which will be filed, with confidential terms redacted, as an exhibit to the Company’s Annual Report on Form 10-K for the period ending on December 31, 2022.

On November 30, 2022, Agenus Inc. (the "Company") entered into an Amendment to Notes, Termination of Warrants and Sale of New Warrants (the "Amendment") with existing noteholders, pursuant to which the Company (Filing, 8-K, Agenus, DEC 2, 2022, View Source [SID1234624738]):

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•
extended the maturity date of the $13.0 million senior subordinated promissory notes previously issued by the Company to such noteholders in 2015 (the "2015 Notes") by two years from February 20, 2023 to February 20, 2025;
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terminated the warrants held by such noteholders to purchase 1,300,000 shares of the Company’s common stock previously issued in 2015;
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terminated the warrants held by such noteholders to purchase 650,000 shares of the Company’s common stock previously issued in 2020; and
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issued to such noteholders new warrants to purchase 1,300,000 shares of the Company’s common stock that will expire February 20, 2026 and issued new warrants to purchase 650,000 shares of the Company’s common stock that will expire February 20, 2028, all such warrants having an exercise price of $2.84 per share, which represented a 15% premium over the 30-day average trailing closing price of the Company’s common stock for the period ending November 9, 2022, and (the "New Warrants").

The foregoing description of the Amendment and the New Warrants do not purport to be complete and are qualified in their entirety by reference to the text of the Amendment and the forms of New Warrants. The Amendment will be filed as an exhibit to the Company’s Annual Report on Form 10-K for the year ended December 31, 2022 and the forms of New Warrants are attached as exhibit 4.1 and 4.2 hereto.

A brief description of the other terms and conditions of the 2015 Notes can be found in Item 2.03 of the Current Report on Form 8-K filed by the Company with the Securities and Exchange Commission on February 26, 2015 and such brief description is incorporated by reference herein.

The securities issued in connection with the Amendment were issued in reliance on the exemption from registration provided by Section 4(2) of the Securities Act of 1933, as amended (the "Securities Act"). Neither the New Warrants nor the underlying shares of common stock have been registered under the Securities Act. Neither the New Warrants nor such underlying shares of common stock may be offered or sold in the United States absent registration or an applicable exemption from registration requirements. No commission or other remuneration was paid or given directly or indirectly for soliciting such issuance.

On December 1, 2022 Evotec partner Kazia Therapeutics Limited ("Kazia", NASDAQ: KZIA; ASX: KZA), an oncology-focused drug development company, reported the publication of positive pre-clinical data for EVT801, a clinical-stage drug candidate currently in a clinical trial for multiple forms of cancer (Press release, Evotec, NOV 30, 2022, View Source [SID1234624732]).

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The publication, by Michael Paillasse and colleagues, summarises a large body of pre-clinical research conducted principally by scientists at Evotec SE and at the University Cancer Institute of Toulouse – Oncopole over a period of several years. It is now published in Cancer Research Communications, a recently-launched journal published by the American Association of Cancer Research ("AACR"). The data formed the basis of Kazia’s in-licensing of EVT801 from Evotec in 2021 and has since supported transition of the compound into an ongoing Phase I clinical trial in patients with advanced solid tumours.

The publication may be accessed via the journal website at
View Source

For further information, please follow this link to the full version of the press release from Kazia Therapeutics.