On March 25, 2024 Theriva Biologics (NYSE American: TOVX), a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need, reported financial results for the full-year ended December 31, 2023, and provided a corporate update (Press release, Theriva Biologics, MAR 25, 2024, View Source [SID1234641417]).

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"With continued advancement of our clinical programs, we have the opportunity to achieve several important milestones this year," said Steven A. Shallcross, Chief Executive Officer of Theriva Biologics. "VIRAGE, our Phase 2b trial of VCN-01 in newly-diagnosed metastatic PDAC remains on track to complete enrollment in the first half of 2024. We completed the first safety review with the IDMC, and with a positive recommendation, VIRAGE will continue to enroll patients as planned with no modifications to the protocol. Our clinical data has demonstrated that repeated systemic dosing of VCN-01 is feasible from a safety perspective, and will now focus on determining whether the repeated-dose regimen of VCN-01 may lead to improved clinical outcomes for patients with PDAC and other solid cancers. In addition to advancing the VIRAGE PDAC trial, we continue to work closely with key opinion leaders, and regulatory agencies to refine our protocol and clinical strategy for VCN-01 as an adjunct to chemotherapy in pediatric patients with advanced retinoblastoma. In parallel, our investigator sponsored Phase 1 trial evaluating the safety and activity of intravitreal VCN-01 in pediatric patients with refractory retinoblastoma continues to progress and will further inform our clinical development pathway in this area of high unmet need."

Recent Program Highlights and Anticipated Milestones:

VCN-01:

Pancreatic Ductal Adenocarcinoma (PDAC): Dosing is underway and enrollment continues to progress for VIRAGE, the randomized, controlled, multicenter, open-label Phase 2b trial of VCN-01 in combination with standard-of-care chemotherapy (gemcitabine/nab-paclitaxel) as a first line therapy in newly diagnosed bmetastatic PDAC patients. The trial is expected to enroll 92 evaluable patients and remains on track to complete enrollment in H1 2024.
The Independent Data Monitoring Committee (IDMC) recommended the continuation of enrollment as planned into the VIRAGE study. According to the IDMC’s expert assessment of clinical data from patients enrolled at six sites open in the U.S. and nine sites in Spain, the ongoing Phase 2b trial will continue without any changes to the protocol. No safety concerns were raised based on the evaluation of data presented at the IDMC meeting. Intravenous VCN-01 has been well tolerated and demonstrated a safety profile consistent with prior clinical trials. Importantly, no additional toxicities were observed in patients receiving a second dose of VCN-01.
Retinoblastoma: The investigator sponsored Phase 1 trial evaluating the safety and activity of intravitreal VCN-01 in pediatric patients with refractory retinoblastoma has completed patient treatment. The trial is designed to evaluate escalating doses of VCN-01 administered by two intravitreal injections separated by 14 days. The investigator sponsored Phase 1 trial, which will complete patient follow-up in H1 2024, will help inform the planned Phase 2 trial design.
This builds on positive preclinical results presented by collaborators at Fundació Sant Joan de Déu demonstrating that administration of VCN-01 in combination with topotecan chemotherapy may improve VCN-01 activity against retinoblastoma.
SYN-004 (ribaxamase):

Dosing is underway for the ongoing Phase 1b/2a randomized, double-blinded, placebo-controlled clinical trial of SYN-004 (ribaxamase) in allogeneic hematopoietic cell transplant (HCT) recipients for the prevention of acute graft-versus-host-disease (aGVHD). SYN-004 appeared to be well tolerated in HCT patients treated with IV meropenem and SYN-004 was not detected in blood samples from the majority of the evaluable patients. The trial is on track to complete enrollment into the second cohort in Q2 2024.
Business Updates

On November 2, 2023, Theriva signed an exclusive option to license intellectual property from Sant Joan de Déu-Barcelona Children’s Hospital (SJD) to explore the therapeutic potential of VCN-01 in combination with topoisomerase I inhibitors. This strengthens a long-term research collaboration with SJD and builds on ongoing trial evaluating VCN-01 in pediatric cancers.
Theriva is actively pursuing licensing discussions for our SYN-020 intestinal alkaline phosphatase asset.
Full-Year Ended December 31, 2023 Financial Results

General and administrative expenses decreased to $7.1 million for the year ended December 31, 2023, from $9.9 million for the year ended December 31, 2022. This decrease of 28% is primarily comprised of the decrease in the fair value of the contingent consideration of $2.8 million, along with lower salary, investor relations, legal costs, consulting fees related to the VCN acquisition, and director and officer insurance offset by higher audit fees, and other consulting fees. The charge relating to stock based compensation expense was $0.4 million for the year ended December 31, 2023, compared to $0.4 million for the year ended December 31, 2022.

Research and development expenses increased to $14.3 million for the year ended December 31, 2023, from $11.7 million for the year ended December 31, 2022. This increase of 22% is primarily the result of higher clinical trial expenses related to our VIRAGE Phase 2 clinical trial of VCN-01 in PDAC, offset by lower expenses related to our Phase 1b/2a clinical trial of SYN-004 (ribaxamase) in allogeneic HCT recipients, the completed Phase 1a clinical trial of SYN-020, decreased manufacturing expenses related to our Phase 1a clinical trial of SYN-020 and lower other indirect costs. We anticipate research and development expense to increase as we continue enrollment in our VIRAGE Phase 2 clinical trial of VCN-01 in PDAC and our ongoing Phase 1 clinical trial in retinoblastoma, expand GMP manufacturing activities for VCN-01, and continue supporting our VCN-11 and other preclinical and discovery initiatives. Research and development expenses also include a charge relating to non-cash stock-based compensation expense of $165,000 for the year ended December 31, 2023, compared to $112,000 for the year ended December 31, 2022. In addition, we expect research and development expenses to increase as we incur higher clinical program costs for our VCN product candidates.

Other income was $1,442,000 for the year ended December 31, 2023, compared to other income of $471,000 for the year ended December 31, 2022. Other income for the year ended December 31, 2023 is primarily comprised of interest income of $1,439,000 and an exchange gain of $3,000. Other income for the year ended December 31, 2022 is primarily comprised of interest income of $512,000 offset by an exchange loss of $41,000.

Cash and cash equivalents totaled $23.2 million as of December 31, 2023, compared to $41.8 million as of December 31, 2022.

The audited financial statements for the year ended December 31, 2023 included in the Company’s Annual Report on Form 10-K contain an unqualified audit opinion from the Company’s independent registered public accounting firm that includes an explanatory paragraph related to the Company’s ability to continue as a going concern.

Conference Call

Theriva Biologics will host a conference call on Monday, March 25, 2024 at 8:30 a.m. ET to discuss its financial results for the full-year ended December 31, 2023 and provide a corporate update. Individuals may participate in the live call via telephone by dialing 1-877-451-6152 (domestic) or 1-201-389-0879 (international) and using the conference ID: 13744453. Participants are asked to dial in 15 minutes before the start of the call to register. Investors and the public can access the live and archived webcast of this call via the "News & Media" section of the company’s website, View Source, under "Events" or by clicking here, up to 90 days after the call.

On March 25, 2024 Syros Pharmaceuticals (NASDAQ:SYRS), a biopharmaceutical company committed to advancing new standards of care for the frontline treatment of hematologic malignancies, reported that the enrollment of 190 patients has been completed in the SELECT-MDS-1 Phase 3 clinical trial evaluating tamibarotene in newly diagnosed higher-risk myelodysplastic syndrome (HR-MDS) patients with RARA gene overexpression (Press release, Syros Pharmaceuticals, MAR 25, 2024, View Source [SID1234641414]). This initial cohort of 190 patients is necessary to support the complete response (CR) primary endpoint analysis. Syros expects to report these pivotal data by the middle of the fourth quarter of 2024.

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"We are pleased to announce the completion of enrollment of the 190 patients necessary to support the primary CR endpoint in SELECT-MDS-1. This marks an important step in advancing tamibarotene through late-stage clinical development and brings us closer to delivering our RARα agonist as a frontline treatment option for the approximately 50 percent of HR-MDS patients with RARA overexpression," said David A. Roth, M.D., Chief Medical Officer of Syros. "We look forward to reporting pivotal data later this year which, if successful, will allow us to file our first New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) and, ultimately, execute on our vision of fundamentally changing the standard of care in hematologic malignancies."

The Phase 3 SELECT-MDS-1 clinical trial is a double-blind, placebo-controlled study evaluating tamibarotene in newly diagnosed HR-MDS patients with RARA overexpression randomized 2:1 to receive tamibarotene in combination with azacitidine or azacitidine alone. The primary endpoint is CR rate in the first 190 patients enrolled in the trial which, together with supporting durability data, can serve as the basis for accelerated approval or full approval; the key secondary endpoint in SELECT-MDS-1 is overall survival (OS) in a total of 550 patients. This study design reflects an efficient "one-trial" approach and could allow SELECT-MDS-1 to serve as a confirmatory study, if needed, to convert from accelerated to full approval. Enrollment is ongoing to reach the 550-patient target.

Syros is also evaluating tamibarotene in combination with venetoclax and azacitidine in the SELECT-AML-1 Phase 2 clinical trial in newly diagnosed unfit acute myeloid leukemia patients with RARA gene overexpression. Syros previously reported initial data from the study, observing a 100% CR/CRi (complete response/complete response with incomplete hematologic recovery) rate in response-evaluable patients treated with the triplet regimen of tamibarotene, venetoclax and azacitidine without increased toxicity, as compared to 70% among patients treated with venetoclax and azacitidine alone. Syros expects to report additional data from SELECT-AML-1 in 2024. Read more here.

On March 25, 2024 Sutro Biopharma, Inc. (Sutro or the Company) (NASDAQ: STRO), a clinical-stage oncology company pioneering site-specific and novel-format antibody drug conjugates (ADCs), reported its financial results for the full year 2023, its recent business highlights, and a preview of select anticipated milestones (Press release, Sutro Biopharma, MAR 25, 2024, View Source [SID1234641413]).

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"The year 2023 was pivotal for Sutro, with the initiation of REFRαME-O1, our registration-directed study of luvelta for platinum-resistant ovarian cancer (PROC) patients, further validating our next-generation ADC capabilities. In addition, we advanced our earlier stage programs, strengthened our management team, and bolstered our already strong cash position with additional non-dilutive capital," said Bill Newell, Sutro’s Chief Executive Officer. "We look forward to continuing the momentum in 2024, with the initiation of a second registration-directed trial with luvelta, REFRαME-P1, for pediatric patients with CBF/GLIS AML, and two additional planned INDs. I am delighted with the strides we are taking towards meaningfully impacting the lives of cancer patients in need."

Recent Business Highlights and Select Anticipated Milestones

STRO-002, International Nonproprietary Name, "luveltamab tazevibulin," abbreviated as "luvelta," FolRα-Targeting ADC Franchise:

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In January 2024, Sutro hosted an investor webcast highlighting luvelta’s broad opportunity to address unmet needs in several FolRα-expressing cancers, including platinum-resistant ovarian cancer (PROC), endometrial cancer, CBFA2T3::GLIS2 (CBF/GLIS; RAM phenotype) acute myeloid leukemia (AML), and non-small cell lung cancer (NSCLC).
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The registration-directed trial, REFRαME-O1, for treatment of PROC is enrolling, with an anticipated ~140 sites in ~20 countries to be opened by the end of 2024. Enrollment of Part 1 of the trial is expected to be completed in the first half of 2024.
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In December 2023, data demonstrating anti-leukemic activity with luvelta, either as a single agent or in combination, in pediatric patients with CBF/GLIS AML, were presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH 2023), including complete remission in 42% of patients with CBF/GLIS AML with ≥5% blasts and in 75% of pediatric patients with CBF/GLIS AML with <5% blasts.
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Enrollment of REFRαME-P1, a registration-enabling trial for pediatric patients with CBF/GLIS AML, is expected to be initiated in the second half of 2024.
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An Investigational New Drug (IND) application submission is planned for treatment of non-small cell lung cancer (NSCLC) in the first half of 2024.
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Continued clinical development is planned in combination with bevacizumab for the treatment of ovarian cancer and in endometrial cancer, as resources permit.

Additional Pipeline Development and Collaboration Updates:

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Sutro plans to submit an IND for STRO-003, a ROR1-targeting ADC, in 2024.
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Sutro plans to submit an IND for STRO-004, a tissue factor-targeting ADC, in 2025.
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Sutro continues to seek to maximize the value of its proprietary cell-free platform by working with partners on programs in multiple disease spaces and geographies and has generated from collaborators an aggregate of approximately $854 million in payments through December 31, 2023, including equity investments.
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In November 2023, Vaxcyte exercised its option to enter into a manufacturing rights agreement with Sutro to obtain control over the development and manufacture of cell-free extract for use under its license agreement with Sutro, including for Vaxcyte’s pneumococcal conjugate vaccine (PCV) franchise, which includes VAX-24 and VAX-31. Upon exercising the option, Vaxcyte paid Sutro $50 million and is obligated to pay Sutro an additional $25 million within six months. Upon the occurrence of certain regulatory milestones, Vaxcyte would be obligated to pay Sutro up to an additional $60 million.
Corporate Updates:

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Sutro continues to build a world-class leadership team through the promotion of Jane Chung to President and Chief Operating Officer, a newly created role in which she will be responsible for driving operational excellence, strategic growth, and overall business success at Sutro.
Full Year 2023 Financial Highlights

Cash, Cash Equivalents and Marketable Securities

As of December 31, 2023, Sutro had cash, cash equivalents and marketable securities of $333.7 million, as compared to $321.1 million as of September 30, 2023, and approximately 0.7 million shares of Vaxcyte common stock with a fair value of $41.9 million, which together provide a projected cash runway into the second half of 2025, based on current business plans and assumptions. Current market conditions provide a challenging financing environment. In this context, Sutro is continuing its process of evaluating its programs and spending.

Unrealized Gain from Increase in Value of Vaxcyte Common Stock

The non-operating, unrealized gain of $9.9 million for the year 2023 was due to the increase since December 31, 2022 in the estimated fair value of Sutro’s holdings of Vaxcyte common stock. Vaxcyte common stock held by Sutro will be remeasured at fair value based on the closing price of Vaxcyte’s common stock on the last trading day of each reporting period, with any non-operating, unrealized gains and losses recorded in Sutro’s statements of operations.

Revenue

Revenue was $153.7 million for the year ended December 31, 2023, as compared to $67.8 million for the same period in 2022, with the 2023 amount related principally to the Vaxcyte manufacturing rights agreement option exercise, Astellas and Merck collaborations, and the recognition of a contingent payment from Tasly. Future collaboration and license revenue under existing agreements, and from any additional collaboration and license partners, will fluctuate as a result of the amount and timing of revenue recognition of upfront, milestones, and other agreement payments.

Operating Expenses

Total operating expenses for the year ended December 31, 2023 were $243.0 million, as compared to $196.7 million for the same period in 2022. The year 2023 includes non-cash expenses for stock-based compensation of $24.9 million and depreciation and amortization of $6.8 million, as compared to $26.3 million and $5.7 million, respectively, in the comparable 2022 period. Total operating expenses for the year ended December 31, 2023 were comprised of research and development expenses of $180.4 million and general and administrative expenses of $62.6 million.

On March 25, 2024 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that the U.S. Food and Drug Administration (FDA) has issued Complete Response Letters (CRLs) for the Biologics License Application (BLA) for odronextamab in relapsed/refractory (R/R) follicular lymphoma (FL) and in R/R diffuse large B-cell lymphoma (DLBCL), each after two or more lines of systemic therapy (Press release, Regeneron, MAR 25, 2024, View Source [SID1234641412]). The only approvability issue is related to the enrollment status of the confirmatory trials. The CRLs – one for R/R FL and one for R/R DLBCL – did not identify any approvability issues with the odronextamab clinical efficacy or safety, trial design, labeling or manufacturing.

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Regeneron has been actively enrolling patients in multiple Phase 3 trials for odronextamab as part of the OLYMPIA program – one of the largest clinical programs in lymphoma. As the OLYMPIA program is intended to change the treatment paradigm of several B-cell non-Hodgkin lymphoma subtypes – including in earlier lines of therapy – in agreeing to the program, the FDA required that the trials include both dose-finding and confirmatory portions. Enrollment in the dose-finding portion has begun, but the CRLs indicate that the confirmatory portions of these trials should be underway and that the timelines to completion be agreed prior to resubmission. Regeneron is committed to working closely with the FDA and investigators to bring odronextamab to patients with R/R FL and R/R DLBCL as quickly as possible. Regeneron plans on sharing updates on enrollment and regulatory timelines later this year.

Regulatory review of odronextamab remains ongoing by the European Medicines Agency (EMA) for the treatment of R/R DLBCL and R/R FL. In the European Union, odronextamab was granted Orphan Drug Designation in DLBCL and FL.

The potential use of odronextamab in R/R DLBCL and R/R FL is currently under clinical development and has not been approved by any regulatory authority.

On March 25, 2024 Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer (NK) cell therapies, reported the pricing of an underwritten offering of 21,010,000 shares of its common stock at a price of $10.00 per share and pre-funded warrants to purchase 3,000,031 shares of common stock (Press release, Nkarta, MAR 25, 2024, View Source [SID1234641411]). The pre-funded warrants are being sold at a price of $9.9999 per warrant, which represents the per share offering price for the common stock less the $0.0001 per share exercise price.

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New and existing investors participated in the offering, including Adage Capital Partners LP, Boxer Capital, Commodore Capital, Cormorant Asset Management, an affiliate of Deerfield Management, EcoR1 Capital, Janus Henderson Investors, OrbiMed, RA Capital Management, Ridgeback Capital Investments, Samsara BioCapital, SR One, and a leading mutual fund.

Gross proceeds to Nkarta from this offering are approximately $240.1 million, before deducting underwriting discounts and commissions and offering expenses. Nkarta intends to use the net proceeds from the offering to fund the continued research and clinical development of NKX019, the continued buildout of internal manufacturing capabilities, and for working capital and for general corporate purposes. The offering is expected to close on or about March 27, 2024, subject to customary closing conditions.

Leerink Partners, TD Cowen, Stifel and Mizuho are acting as joint bookrunners for the offering.

All securities in the offering are to be issued and sold by Nkarta. The offering was conducted pursuant to a shelf registration statement (File No. 333-270680), which was initially filed with the Securities and Exchange Commission ("SEC") on March 17, 2023 and declared effective by the SEC on May 5, 2023. The offering was made only by means of a prospectus supplement and accompanying prospectus describing the terms of the offering. Copies of the prospectus supplement and the accompanying prospectus relating to this offering may be obtained by contacting the following: Leerink Partners LLC, Syndicate Department, 53 State Street, 40th Floor, Boston, MA 02109, or by telephone at (800) 808-7525 ext. 6105, or by email at [email protected]; Cowen and Company, LLC, 599 Lexington Avenue, New York, NY 10022, by telephone at (833) 297-2926, or by email at [email protected]; Stifel, Nicolaus & Company, Incorporated, Attention: Prospectus Department, One Montgomery Street, Suite 3700, San Francisco, CA 94104, by telephone at (415) 364-2720 or by email at [email protected]; Mizuho Securities USA LLC, Attention: Equity Capital Markets, 1271 Avenue of the Americas, 3rd Floor, New York, New York 10020, by telephone at (212) 205-7602 or by email at [email protected]. These documents may also be obtained for free on the SEC’s website located at View Source

This press release does not constitute an offer to sell or the solicitation of an offer to buy the securities described herein, nor shall there be any offer, solicitation or sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.