On December 14, 2023 Syndax Pharmaceuticals, Inc. ("Syndax" or the "Company") (Nasdaq: SNDX), a clinical-stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported the pricing of an underwritten public offering of 10,810,810 shares of its common stock (Press release, Syndax, DEC 14, 2023, View Source [SID1234638616]). The public offering price of each share of common stock is $18.50. The aggregate gross proceeds from this offering are expected to be approximately $200.0 million, before deducting underwriting discounts and commissions and other offering expenses payable by Syndax. In addition, Syndax granted the underwriters a 30-day option to purchase up to an additional 1,621,621 shares of common stock. All of the shares of common stock are being sold by Syndax. The offering is expected to close on December 19, 2023, subject to customary closing conditions.

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Goldman Sachs & Co. LLC, J.P. Morgan, TD Cowen and Stifel are acting as joint book-running managers for the offering. B. Riley Securities is acting as manager for the offering.

The shares are being offered pursuant to an automatically effective "shelf" registration statement previously filed with the Securities and Exchange Commission ("SEC"). A preliminary prospectus supplement and accompanying prospectus relating to the offering have been filed with the SEC and are available on the website of the SEC at www.sec.gov. A final prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC. When available, copies of the final prospectus supplement and accompanying prospectus relating to the offering may be obtained from: Goldman Sachs and Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, telephone: 866-471-2526, facsimile: 212-902-9316 or by emailing [email protected]; J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, telephone: (866) 803-9204, or by emailing [email protected]; or Cowen and Company, LLC, 599 Lexington Avenue, New York, NY 10022, by emailing [email protected] or by telephone at (833) 297-2926; or Stifel, Nicolaus & Company, Incorporated, Attention: Prospectus Department, One Montgomery Street, Suite 3700, San Francisco, California 94104, by telephone at (415) 364-2720 or by emailing [email protected].

This press release shall not constitute an offer to sell, or the solicitation of an offer to buy, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. Any offer, if at all, will be made only by means of a prospectus supplement and accompanying prospectus, which are a part of the effective registration statement.

On December 14, 2023 Schrödinger (Nasdaq: SDGR), whose physics-based computational platform is transforming the way therapeutics and materials are discovered, reported a detailed review of its proprietary drug discovery and development programs during its Pipeline Day today, from 10:00 a.m. – 12:30 p.m. ET (Press release, Schrodinger, DEC 14, 2023, View Source [SID1234638587]).

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"We are excited to share our first clinical data for a proprietary Schrödinger program, SGR-1505, and to outline the opportunities emerging from our broad portfolio of drug discovery programs in multiple therapeutic areas, including oncology, immunology and neurology," stated Karen Akinsanya, Ph.D., president of R&D, therapeutics at Schrödinger. "Our therapeutics team has been very productive since we started building this portfolio. With two programs in the clinic, multiple programs in late discovery and preclinical development, and our advancing collaborations, we believe the future of our therapeutics portfolio is very promising."

SGR-1505 Clinical Progress and Program Update

During Pipeline Day, Schrödinger is presenting new data showing that its novel MALT1 inhibitor, SGR-1505, was well tolerated in a Phase 1 study of 73 healthy volunteers. No drug-related serious adverse events or dose limiting toxicities were observed in the study. In the study, SGR-1505 achieved greater than 90 percent inhibition of IL-2 secretion in activated T cells, confirming target engagement and meeting the pharmacodynamic goals for the study. The data support continued evaluation of SGR-1505 in the ongoing Phase 1 study in patients with relapsed or refractory B-cell malignancies.

"The data presented from our successful healthy volunteer study demonstrate that SGR-1505 is well-tolerated with a pharmacokinetic and pharmacodynamic profile that supports continued development," stated Margaret Dugan, M.D., chief medical officer at Schrödinger. "These data add significantly to our understanding of SGR-1505 and inform our clinical development strategy in hematologic malignancies. The SGR-1505 program is progressing well, and we look forward to continued enrollment in the patient study and reporting initial data in late 2024 or 2025."

Schrödinger is also presenting preclinical data for SGR-1505 demonstrating that SGR-1505 has favorable attributes and the potential for combination activity with standard-of-care agents in B cell malignancies. These data were presented earlier this week at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

Three New Programs: EGFRC797S, PRMT5-MTA and NLRP3

Schrödinger is presenting three new proprietary discovery programs at Pipeline Day, targeting EGFRC797S, PRMT5-MTA and NLRP3.

EGFR inhibitors are first-line standard of care agents for advanced non-small cell lung cancer patients with activating EGFR mutations, but relapse often occurs due to the development of resistance mutations, including EGFRC797S. Schrödinger has identified multiple EGFRC797S inhibitors and is advancing wild-type sparing, double mutant CNS-penetrant inhibitors with the potential to address brain metastases in patients whose disease progresses following first-line treatment, and to potentially achieve deeper, more durable responses through new combination regimens.

PRMT5-MTA inhibition has demonstrated clinical responses in both hematologic and solid tumors with improved safety versus PRMT5 inhibitors due to a synthetic lethal targeting of cancer cells with MTAP-deletions. Schrödinger has identified selective, potent PRMT5-MTA inhibitors with potential applications in solid tumors, brain metastases and primary CNS tumors.

NLRP3 is a validated target, and mutations in the NLRP3 gene are associated with a broad spectrum of inflammatory and auto-immune diseases. Schrödinger has identified structurally distinct, selective, NLRP3 inhibitors with anti-inflammatory activity in preclinical models, and is continuing to optimize peripheral and brain-penetrant leads.

Broad Portfolio Addresses Synthetic Lethality and DNA-Damage Repair

Schrödinger is advancing multiple oncology programs designed to exploit the intrinsic vulnerabilities of cancer cells through synthetic lethality and inhibition of DNA-damage repair. Today, the company is discussing its synthetic lethality programs, PRMT5-MTA and SGR-3515 (Wee1/Myt1). The company is also reviewing SGR-2921, which targets CDC7, a key regulator of replication stress and DNA-damage repair.

Schrödinger is reporting preclinical data showing that SGR-3515 has a differentiated biochemical, biophysical and functional profile, with sustained inhibition of Wee1 and Myt1 in tumor cells. Concurrent loss of function of Wee1 and Myt1 confers selective vulnerability in cancer cells and could offer increased anti-tumor activity. SGR-3515 has potential to treat a broad range of solid tumors, including uterine and ovarian cancers. Schrödinger plans to submit an IND for SGR-3515 in the first half of 2024.

Schrödinger is also discussing preclinical data presented at ASH (Free ASH Whitepaper) demonstrating that SGR-2921 exhibited better activity compared to other CDC7 inhibitors, and showed anti-proliferative effects in treatment-resistant acute myeloid leukemia (AML) patient-derived samples, as well as reduction of blasts in multiple AML models. A Phase 1 study of SGR-2921 is ongoing in patients with AML or myelodysplastic syndrome, and the company expects to report initial data from the study in late 2024 or 2025.

"CDC7 is a promising therapeutic target for the treatment of myelodysplastic syndromes and acute myeloid leukemia, diseases for which there is a significant unmet need in treating both frontline and relapsed/refractory patients," stated Elie Traer, M.D., Ph.D., associate professor at the Center for Hematologic Malignancies at Oregon Health & Science University. "Targeting CDC7 with emerging investigational therapeutics, such as SGR-2921, represents an opportunity to expand our armamentarium of treatment options beyond existing targeted therapies."

Anticipated Milestones

Today, Schrödinger outlined the anticipated milestones for its proprietary pipeline:

Report initial data from the Phase 1 study of SGR-1505 in late 2024 or 2025
Report initial data from the Phase 1 study of SGR-2921 in late 2024 or 2025
Submit IND for SGR-3515 in the first half of 2024 and initiate a Phase 1 study in 2024
Submit an IND from its discovery portfolio in 2025
Event Information

Schrödinger’s Pipeline Day will begin at 10:00 a.m. ET and is expected to conclude at approximately 12:30 p.m. ET. The live presentation can be accessed in the "Investors" section of Schrödinger’s website and will be archived for approximately 90 days. To participate in the live webcast, please register for the event here. It is recommended that participants register at least 15 minutes in advance of the event.

On December 14, 2023 AnHeart Therapeutics ("AnHeart"), a global clinical-stage biopharmaceutical company developing novel precision therapies for people with cancer and Foundation Medicine, Inc., reported that the companies have entered a strategic collaboration for the development and regulatory approval of Foundation Medicine’s tissue-based and liquid-based comprehensive genomic profiling tests, FoundationOneCDx and FoundationOneLiquid CDx, as companion diagnostics for AnHeart’s investigational next-generation ROS1 inhibitor, taletrectinib, in the United States (Press release, AnHeart Therapeutics, DEC 14, 2023, View Source [SID1234638586]).

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Taletrectinib is a potential best-in-class ROS1 inhibitor being evaluated for the treatment of patients with advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC), an underserved group of lung cancer patients in need of new options. Taletrectinib has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration.

"We are excited to collaborate with Foundation Medicine on the development of both tissue- and liquid-based companion diagnostics to help identify patients who may benefit from taletrectinib," said Lian Li, MD, PhD, AnHeart’s U.S. Chief Medical Officer. "Foundation Medicine’s high-quality testing portfolio and proven regulatory expertise makes them a preferred partner for us as we work to bring this promising next-generation therapy to patients living with ROS1-positive NSCLC."

Foundation Medicine’s portfolio of FDA-approved diagnostic tests offer physicians both blood- and tissue-based testing options for detecting genomic alterations that help guide personalized treatment decisions. Foundation Medicine is the global leader in companion diagnostic approvals. The company has approximately 60% of all U.S. companion diagnostic approvals for next-generation sequencing (NGS) testing.

"High-quality genomic profiling tests are critical to inform treatment decisions and have become foundational for treating NSCLC as more precision therapies targeting specific genetic alterations, such as ROS1, are being developed," said Troy Schurr, Chief Biopharma Business Officer at Foundation Medicine. "We look forward to working with AnHeart to deliver swift access to this investigational precision therapy if approved and ultimately to help more patients living with this disease."

About Taletrectinib

Taletrectinib is an investigational oral, potent, brain penetrant, selective, next-generation ROS1 inhibitor being evaluated for the treatment of ROS1-positive NSCLC.

AnHeart is evaluating taletrectinib in patients with advanced or metastatic ROS1-positive NSCLC in two pivotal Phase 2 trials, TRUST-I (NCT04395677) in China, and TRUST-II (NCT04919811), a global pivotal trial.

In 2023, AnHeart reported positive interim data from both Phase 2 trials. In both trials, interim results showed taletrectinib shrank tumors by more than 30% in more than 90% of patients with ROS1-positive NSCLC who had not previously received a ROS1 TKI (TKI naïve) and in more than 50% of patients who had previously received a ROS1 TKI (TKI pre-treated), and the responses were durable. Taletrectinib also showed robust intracranial activity in the subgroup of patients with disease that had spread to the brain and in those who had developed resistance mutations to previous ROS1 treatment. Taletrectinib was generally well tolerated with a low incidence of neurological adverse events.

About FoundationOneCDx

FoundationOne CDx is a next-generation sequencing based in vitro diagnostic device for detection of substitutions, insertion and deletion alterations (indels), and copy number alterations (CNAs) in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) using DNA isolated from formalin-fixed, paraffin-embedded (FFPE) tumor tissue specimens. FoundationOne CDx is for prescription use only and is intended as a companion diagnostic to identify patients who may benefit from treatment with certain targeted therapies in accordance with their approved therapeutic product labeling. Additionally, FoundationOne CDx is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology for patients with solid malignant neoplasms. Use of the test does not guarantee a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. Some patients may require a biopsy. For a full list of targeted therapies for which FoundationOne CDx is indicated as a companion diagnostic, please visit View Source

About FoundationOneLiquid CDx

FoundationOne Liquid CDx is a qualitative next generation sequencing based in vitro diagnostic test for prescription use only that uses targeted high throughput hybridization-based capture technology to analyze 324 genes utilizing circulating cell-free DNA (cfDNA) isolated from plasma derived from anti-coagulated peripheral whole blood of advanced cancer patients. The test is FDA-approved to report short variants in over 300 genes and is a companion diagnostic to identify patients who may benefit from treatment with specific therapies (listed in Table 1 of the Intended Use) in accordance with the approved therapeutic product labeling. Additional genomic findings may be reported and are not prescriptive or conclusive for labeled use of any specific therapeutic product. Use of the test does not guarantee a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. Patients who are negative for companion diagnostic mutations should be reflexed to tumor tissue testing and genomic alteration status confirmed using an FDA-approved tumor tissue test, if feasible. For the complete label, including companion diagnostic indications and complete risk information, please visit www.F1LCDxLabel.com.

About ROS1-Positive NSCLC

Approximately 200,000 people are anticipated to be diagnosed with non-small cell lung cancer (NSCLC), the most common form of lung cancer, in the United States in 2023. It is estimated that approximately 1-2% of people with NSCLC are ROS1-positive. Up to 35% of people newly diagnosed with metastatic ROS1-positive NSCLC have tumors that have spread to their brain (brain metastases), increasing up to 55% for those whose cancer has progressed following initial treatment. While people with other types of lung cancer have seen great advances, there has been limited progress for people with ROS1-positive NSCLC who remain in need of new options.

On December 14, 2023 TME Pharma N.V. (Euronext Growth Paris: ALTME), a biotechnology company focused on developing novel therapies for treatment of cancer by targeting the tumor microenvironment (TME), reported that it has successfully completed its capital increase with preferential subscription rights through the issuance of new shares with associated warrants for an amount of €2.7 million (the "Rights Issue") (Press release, TME Pharma, DEC 14, 2023, View Source [SID1234638585]).

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"We are very grateful to all our investors for their participation in this latest successful financing for TME Pharma, which we are convinced offers a great opportunity and one which I have subscribed to1," said Aram Mangasarian, CEO of TME Pharma. "We extend our thanks to our existing shareholders to whom we offered the opportunity to minimize their dilution linked to this capital raise by providing preferential subscription rights. We are thrilled to see their significant participation and consider it a sign of strong support for the company. And we warmly welcome our new investors who are joining us at the beginning of a crucial period in our mission of developing our lead asset NOX-A12 in brain cancer. I’m pleased to report that this capital injection provides sufficient flexibility to finalize our formal advice meeting with the FDA on the next clinical and regulatory steps for NOX-A12, file our IND and expedited regulatory pathway applications and allows us to step up the search for potential partners to collaborate with us in bringing NOX-A12 to market in the fastest, most efficient way possible."

Following the subscription period from November 30 to December 11, 2023, total subscription orders amounted to 5,076,880 ABSA Y for an amount of €1,269,220, representing a subscription rate of 46.9%. Subscriptions on an irreducible basis represented 4,542,295 ABSA Y for €1,135,573.75. Subscriptions on a reducible basis represented 334,585 ABSA Y for €83,646.25. Free subscriptions represented 200,000 ABSA Y for €50,000. Considering the number of ABSA Y subscribed for at the end of the period, €1,437,162 corresponding to 5,748,648 ABSA Y was guaranteed by a group of Dutch investors in line with their commitment to bring the capital increase to the total amount of €2.7 million gross.

The gross proceeds of the Rights Issue amounted to €2.7 million and resulted in the issuance of 10,825,528 ABSA Y (containing 10,825,528 new shares and 10,825,528 Warrants Y) subscribed at a price of €0.25. Settlement and delivery of the new shares and the attached Warrants Y, as well as their admission to trading on Euronext Growth Paris, are scheduled for December 18, 2023. The new shares will be listed on the same quotation line as the existing shares, under ISIN code NL0015000YE1, and the Warrant Y will be listed on a separate quotation line under ISIN code NL0015001SS1. Warrants Y have maturity period until February 16, 2024, with two periods of exercise: from January 10 to January 16, 2024, and from February 12 to February 16, 2024. Each 5 Warrants Y entitle the holder to subscribe to 2 ABSA Z (2 new shares with 2 Warrants Z attached). Each series of 4 Warrants Z entitle the holder to subscribe to 5 new shares with an exercise price of €0.20 per Warrant Z and a maturity of June 30, 2025, with one period of exercise per quarter. See a dedicated "TME Rights Issue" page on the company’s website for further details.

Considering the net proceeds of the Rights Issue and based on the company’s current budget projections, the company’s cash runway extends into May 2024. The net proceeds from this operation will primarily be used:

to reach increased data maturity in the ongoing NOX-A12 GLORIA Phase 1/2 trial in glioblastoma and to advance discussions with the US Food and Drug Administration (FDA) past regulatory milestones (approx. 1/3rd of proceeds)
for general corporate purposes including intensifying interactions with investors and potential industry partners (approx. 1/3rd of proceeds)
to buy back 898 out of 1,998 outstanding convertible bonds previously issued under agreement with Atlas Special Opportunities and subject the remaining convertible bonds to a lock-up until April 1, 2024 (approx. 1/3rd of proceeds)
The table below summarizes the maximum dilutive potential for an investor who did NOT participate in the transaction should all Warrants Y and all Warrants Z be exercised, and excluding any potential additional dilution. Shareholders who participate fully in the transaction, i.e. who purchased the ABSA Y and subsequently exercise both Warrants Y and Z will not be diluted by this transaction.

Description

Shares to be issued

Total shares outstanding

Dilution (max)

Shareholder starting with 1% would then hold

Issue of ABSA Y from the capital increase
(Dec 18, 2023)

10,825,528

17,320,845

62.50%

0.38%

Exercise of Warrant Y
(latest on Feb 16, 2024)

4,330,211

21,651,057

70.00%

0.30%

Exercise of Warrant Z
(latest on June 20, 2025)

5,412,764

27,063,821

76.00%

0.24%

For more information on the Rights Issue, please consult the Rights Issue dedicated section on the TME Pharma website.

On December 14, 2023 Nona Biosciences, a global biotechnology company providing a total solution from "Idea to IND" (I to ITM), ranging from target validation and antibody discovery through preclinical research, reported that it has entered into an exclusive license agreement with Pfizer Inc. for the global clinical development and commercialization of Nona Biosciences’ MSLN-targeted antibody-drug conjugate (ADC), HBM9033 (Press release, Nona Biosciences, DEC 14, 2023, View Source [SID1234638583]).

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Under the terms of the agreement, Nona Biosciences will receive a total of up to $53 million in upfront and near-term payments, with the potential for additional payments of up to $1.05 billion upon achieving certain development and commercial milestones. Nona Biosciences is also eligible to receive tiered royalties on net sales ranging from high single digits to high teens.

"We are delighted to collaborate with Pfizer, a company that is committed to developing high-impact medicines for people living with cancer," said Jingsong Wang, M.D., Ph.D., Chairman of Nona Biosciences. "This agreement represents a significant milestone in the advancement of our proprietary Harbour Mice platform and the ADC ecosystem, affirming Nona’s robust capabilities and expertise in antibody discovery and development. This partnership with Pfizer further enhances Nona’s global network of collaborations through innovative models, thereby amplifying the scientific and commercial value of our technology platforms."

About HBM9033

HBM9033 is an ADC drug that specifically targets human MSLN, a tumor-associated antigen (TAA) upregulated in various solid tumors. The fully human monoclonal antibody (mAb) in HBM9033 is derived from the Harbour Mice platform and possesses well-tuned properties, exhibiting reduced binding to shedding MSLN (sMSLN) while maintaining strong binding and internalization to membrane-bound MSLN. The unique design of the mAb ensures superior potency and safety in various preclinical tumor models with differing MSLN expression levels, positioning HBM9033 as a potential globally best-in-class therapeutic option.