On April 1, 2024 Quince Therapeutics, Inc. (Nasdaq: QNCX), a late-stage biotechnology company developing an innovative drug delivery technology designed to leverage a patient’s own biology to deliver rare disease therapeutics, reported an update on the company’s development pipeline and announced financial results for the fourth quarter and fiscal year ended December 31, 2023 (Press release, Quince Therapeutics, APR 1, 2024, View Source [SID1234641658]).

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"With the acquisition of EryDel S.p.A. in October last year, we have successfully shifted our strategic focus to become a Phase 3 biotechnology company dedicated to securing regulatory approval for our lead product, EryDex, for the treatment of patients with Ataxia-Telangiectasia (A-T)," said Dirk Thye, M.D., Quince’s Chief Executive Officer and Chief Medical Officer. "With $75.1 million cash on hand, we expect to have sufficient funding to complete our Phase 3 clinical trial, in addition to supporting the expansion of EryDex into other indications and our Autologous Intracellular Drug Encapsulation (AIDE) technology platform into new products. By pioneering the delivery of drugs encapsulated in a patient’s own red blood cells, we are working to redefine the standard of care, first for chronic corticosteroid therapy, and later for other drugs, that will meaningfully improve the quality of life for rare disease patients."

Pivotal Phase 3 NEAT Clinical Trial

Completed the majority of study start up activities related to the company’s pivotal Phase 3 NEAT (Neurologic Effects of EryDex on Subjects with A-T; IEDAT-04-2022/NCT06193200) clinical trial.
NEAT is an international, multi-center, randomized, double-blind, placebo-controlled study to evaluate the neurological effects of the company’s lead asset, EryDex (dexamethasone sodium phosphate [DSP] encapsulated in autologous red blood cells), in patients with A-T.
On track to meet expectations to begin enrollment in the NEAT study during the second quarter of 2024.
Pivotal Phase 3 NEAT clinical trial will be conducted under a Special Protocol Assessment (SPA) agreement with the U.S. Food & Drug Administration (FDA).
Plan to enroll approximately 86 patients with A-T ages six to nine years old (primary analysis population) and approximately 20 patients with A-T ages 10 years or older.
Participants will be randomized (1:1) between EryDex or placebo and treatment will consist of six infusions scheduled once every 21 to 30 days. The primary efficacy endpoint will be measured by the change from baseline to last visit completion in rescored modified International Cooperative Ataxia Rating Scale (RmICARS).
Participants who complete the full treatment period, complete study assessments, and provide informed consent will be eligible to transition to an open label extension study.
Expect to report Phase 3 NEAT topline results in the second half of 2025 with a potential NDA submission in 2026, assuming positive study results.
Quince estimates there are an aggregate of approximately 10,000 patients with A-T in the U.S., U.K., and EU4 countries.
There are currently no approved therapeutic treatments for A-T and the market represents a $1+ billion peak commercial opportunity globally based on the company’s internal estimates and assumptions.
Scientific, Pipeline, and Corporate Updates

Detailed EryDex’s optimized delivery of DSP encapsulated in red blood cells with a comparison of company data relative to published corticosteroid pharmacokinetic and biodistribution information. Red blood cells have several characteristics that make them a potentially ideal vehicle for drug delivery, including potentially better tolerability, enhanced tissue distribution, reduced immunogenicity, and prolongation of circulating half-life. Learn more here.
Intend to investigate other potential indications for EryDex where chronic corticosteroid treatment is – or has the potential to become – a standard of care if there were not corticosteroid-related safety concerns. This evaluation process is expected to span across ataxias, neuromuscular indications, hematology, cancer, and autoimmune diseases, with a focus on rare diseases.
Plan to evaluate additional potential applications of Quince’s proprietary AIDE technology platform using drugs and biologics targeted at rare and debilitating diseases to further expand the company’s drug development pipeline.
Targeting participation at several A-T related global ataxia and neurology scientific congresses in 2024, in addition to ongoing engagement of global patient advocacy groups as enrollment of the Phase 3 NEAT study progresses.
Strong Cash Position Expected to Support Meaningful Clinical Milestone

Reported $75.1 million in cash, cash equivalents, and short-term investments as of December 31, 2023. Quince expects its existing cash runway to be sufficient to fund the company’s capital efficient development plan into 2026.
Expect to fully fund lead asset, EryDex, through Phase 3 NEAT topline results and prepare for a potential NDA submission in 2026, assuming positive study results. This includes approximately $20 million for the NEAT study and approximately $15 million in direct trial costs for the open label extension.
Evaluate potential strategic partnerships to out-license ex-U.S. regional territories to extend operational runway to support potential NDA approval of EryDex, as well as further advance other potential indications and programs discovered using the AIDE platform.

On April 1, 2024 Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company working to develop the world’s most potent vaccines, reported that it has commenced an underwritten public offering of shares of its common stock (or pre-funded warrants to purchase common stock in lieu thereof) and accompanying common warrants to purchase common stock (or pre-funded warrants to purchase common stock in lieu thereof) (Press release, Gritstone Bio, APR 1, 2024, View Source [SID1234641657]). All of the shares of common stock, pre-funded warrants and accompanying common warrants are being offered by Gritstone bio. The proposed offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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TD Cowen and Evercore ISI are acting as the joint book-running managers for the proposed offering.

The securities are being offered by Gritstone bio pursuant to a registration statement on Form S-3 (File No. 333-263455) previously filed and declared effective by the Securities and Exchange Commission ("SEC"). A preliminary prospectus supplement and accompanying base prospectus relating to and describing the terms of the proposed offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. Copies of the preliminary prospectus supplement and accompanying base prospectus may also be obtained, when available, from: TD Securities (USA) LLC, 1 Vanderbilt Avenue, New York, NY 10017, by telephone at (855) 495-9846 or by email at [email protected]; or Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, 35th Floor, New York, New York 10055, by telephone at (888) 474-0200, or by email at [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.

On April 1, 2024 Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company working to develop the world’s most potent vaccines, reported positive preliminary data from the ongoing, signal seeking Phase 2 portion of the Phase 2/3 study evaluating GRANITE, its personalized neoantigen cancer vaccine, in front-line metastatic microsatellite stable colorectal cancer (MSS-CRC) (Press release, Gritstone Bio, APR 1, 2024, View Source [SID1234641656]). The randomized, controlled, open-label study is designed to quantify the clinical benefit of maintenance therapy with GRANITE (GRT-C901/GRT-R902) in combination with immune checkpoint blockade in addition to fluoropyrimidine/bevacizumab versus fluoropyrimidine/bevacizumab alone. Overall progression free survival (PFS) data show an early trend in benefit for GRANITE patients (HR=0.82, [95% CI, 0.34-1.67]; 62% censored) and extended PFS benefit in high-risk patients (HR=0.52 [95% CI, 0.15-1.38]; 44% censored), in whom progression occurs faster. Circulating tumor DNA (ctDNA) analysis over several months of treatment shows the expected relationship with disease progression and favors GRANITE, while short-term ctDNA response analysis (molecular response as defined per protocol) did not demonstrate a difference between study arms. Gritstone bio successfully manufactured GRANITE product candidate for every eligible patient (i.e., 100% vaccine manufacturing success rate).

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"Today’s preliminary Phase 2 results are highly encouraging and represent the first randomized trial evidence, albeit early, that a personalized neoantigen-directed vaccine can potentially drive efficacy in a metastatic ‘cold’ tumor. The overall trend of PFS improvement in GRANITE recipients is great to see, and the exploratory PFS hazard ratio of 0.52 in the high-risk group, a more mature dataset, is a striking signal," said Andrew Allen, MD, PhD, Co-founder, President & CEO of Gritstone bio. "Pioneering new spaces carries inherent risks, and with regard to defining molecular response, we simply got it wrong. ctDNA levels in both arms decreased on chemotherapy for longer than we anticipated, generating similar short-term molecular response rates across arms and rendering our protocol measure of ctDNA change uninformative. Fortunately, long-term analysis demonstrates the expected correlation of ctDNA with clinical benefit and favors GRANITE patients. We believe these preliminary findings put us in a strong position to share mature PFS data in the third quarter and then enter regulatory discussions regarding Phase 3. The growing body of evidence favoring GRANITE in this trial, including positive PFS and long-term ctDNA trends in both high and low-risk populations, is exciting and suggests GRANITE is working in this notoriously underserved patient population."

"Up to 97% of patients with metastatic colorectal cancer, the second most common cause of cancer death, are MSS. Unlike patients with melanoma and lung cancer, they have not benefited from standard immunotherapies such as checkpoint inhibitors. These preliminary results indicate that GRANITE is inducing a potentially significant immune response in a disease that has been felt to be immunologically cold," said J. Randolph Hecht, MD, Professor of Clinical Medicine and Director of the UCLA GI Oncology Program and an investigator in the GRANITE Phase 2/3 study. "The PFS difference, particularly in a poor prognosis group of patients, indicates the potential for clinical benefit and provides the rationale for a confirmatory Phase 3 trial, about which I am very excited. Furthermore, we are learning how to better analyze ctDNA continuously to study the efficacy of this novel immunotherapy. Expanding the scope of immunotherapy to a broader spectrum of cancer patients is the ‘holy grail’ of oncology, especially for MSS colorectal cancer. While early, these promising results suggest GRANITE has potential to deliver clinically meaningful benefit in MSS-CRC and other cold tumors."

Key Findings from Preliminary Phase 2 Data in Front-Line Metastatic MSS-CRC
Clinical data cut as of March 8, 2024; ctDNA data cut as of March 12, 2024

One hundred and four (104) patients were randomized (1:1) in the study: Sixty-seven (67) patients (39 GRANITE arm, 28 control arm) are included in the treated analysis below. Thirty-six patients have left the study prior to randomized treatment primarily due to early progressive disease or withdrawal of consent, and one patient has yet to begin study treatment start. Demographics and clinical characteristics were balanced between arms (stage, sidedness, presence of liver metastases), with approximately 75% of patients having liver metastases.

Progression Free Survival (PFS)

Early trend in PFS benefit was observed for GRANITE recipients
Hazard ratio of 0.82 ([95% CI, 0.34-1.67]; 62% censored) in all patients
Hazard ratio of 0.52 ([95% CI, 0.15-1.38]; 44% censored) in high-risk patients1 (>90% have liver metastases). Median PFS of 12 months (GRANITE) vs. 7 months (control).
1High-risk subgroup defined as baseline ctDNA above the median value (2%) for the control group (ctDNA quantified as mean variant allele frequency [VAF] at time of study randomization). This analysis was performed on 44 patients who received study treatment (control and GRANITE arms) and have available baseline ctDNA data.
GRANITE and control arms begin separating 1-2 months after initiation of GRANITE treatment, consistent with expected kinetics of GRANITE-induced immune response
Biomarker Results – Circulating Tumor DNA (ctDNA)

Short-term molecular response (>30% reduction in ctDNA using single time-point analysis, defined per protocol) is uninformative due to unanticipated continuation of ctDNA drop beyond induction chemotherapy.
Molecular response, similar in both arms (30% [6/20] in vaccine arm; 42% [5/12] in control arm)
Long-term ctDNA responses align with PFS trends and favor GRANITE vs. control patients
Analysis in the high-risk group1 shows that between first blood draw (time of randomization) and last blood draw (most recent study visit), ctDNA shifted from high (>2% VAF) to low (≤2% VAF) in 56% (9/16) of GRANITE patients vs 22% (2/9) of control patients. Progressive disease was observed in 44% (7/16) vs 78% (7/9), respectively, within this group.
Analysis in patients whose ctDNA was negative after induction chemotherapy, a low-risk group, favors GRANITE. Sustained ctDNA negativity was observed in 67% (6/9) of GRANITE recipients vs 38% (3/8) control patients. Progressive disease was observed in 11% (1/9) and 38% (3/8) of these patients, respectively.
Safety and Tolerability

GRANITE demonstrated a favorable safety and tolerability profile
Vast majority of adverse events (AEs) were Grade 1/2
Common AEs were mild systemic and local effects typically associated with any potent vaccine (i.e., transient flu-like illness)
No patients discontinued study treatment due to an AE
A presentation reviewing these results has been added to the Presentations page of Gritstone’s website, View Source

On April 1, 2024 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported an oral presentation at the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 2024 Annual Meeting, taking place May 7 – 11, 2024, in Baltimore, MD and virtually (Press release, CRISPR Therapeutics, APR 1, 2024, View Source [SID1234641655]).

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Title: Development of an In Vivo Non-Viral Ocular Editing Platform and Application to Potential Treatments for Glaucoma
Session Type: In-Person Oral Presentation
Session Title: Ophthalmic and Auditory: Delivery Innovations
Abstract Number: 87
Location: Room 318 – 323
Session Date and Time: Wednesday, May 8, 2024, 1:30 p.m. – 3:15 p.m. ET

Abstracts will be released to the public on April 22, 2024, at 4:30 p.m. ET at View Source The data are embargoed until 6:00 a.m. ET on the presentation day, Wednesday May 8, 2024. A copy of the presentation will be available at www.crisprtx.com once the presentation concludes.

On April 1, 2024 CNS Pharmaceuticals, Inc. (NASDAQ: CNSP) ("CNS" or the "Company"), a biopharmaceutical company specializing in the development of novel treatments for primary and metastatic cancers in the brain and central nervous system, reported its financial results for the full year ended December 31, 2023 and outlined recent corporate and clinical development highlights (Press release, CNS Pharmaceuticals, APR 1, 2024, View Source [SID1234641654]).

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John Climaco, CEO of CNS Pharmaceuticals, stated, "There remains a tremendous unmet medical need for an effective treatment for GBM, and we are dedicated to advancing this important program forward to bring much needed hope for patients. Over the course of 2023 we made significant progress with our lead development program, Berubicin, having recently achieved four primary objectives toward which we were actively working: maintain a rapid pace of enrollment to reach our pre-planned interim analysis; complete planned enrollment; bolster buy-in from investigators; and expand our board indicating a strong support system from industry leaders."

"In addition to reaching complete enrollment we have also successfully completed the interim futility analysis and received a recommendation from the independent Data Safety Monitoring Board (DSMB) to continue the study without modification, which we believe is a monumental step towards our objective of seeing Berubicin approved. Additionally, we have added noteworthy members to our Board who have the knowledge and expertise to help drive our efforts forward. With these achievements behind us, we are closer to fulfilling our mission and promise to patients and shareholders to bring Berubicin across the finish line towards approval," concluded Mr. Climaco.

Recent Achievements

· Closed a public offering for gross proceeds of $4.0 million;
· Appointed biotech commercialization leader Amy Mahery to the Company’s Board of Directors;
· Announced successful outcome to the pre-planned interim futility analysis of efficacy and safety in the Company’s ongoing global, potentially pivotal trial of Berubicin for the treatment of GBM; and
· Reached full enrollment in study of Berubicin for the treatment of GBM.

Berubicin Clinical Development Progress

The trial design of our potentially pivotal trial of Berubicin included a pre-planned, non-binding interim futility analysis. The Company reached the criteria required by the study protocol to conduct this interim futility analysis, which an independent DSMB is responsible for conducting. The DSMB’s charter mandated that they review the primary endpoint, Overall Survival, as well as secondary endpoints and safety data to determine whether the efficacy data for the risk-benefit profile warrants modification or discontinuation of the study. On December 18, 2023, the Company released the DSMB’s recommendation which was to continue the study without modification. Management remains blinded to the data underlying the recommendation of the DSMB.

The Company expects to report topline data from its study of Berubicin in the first half of 2025, although it is impossible to accurately predict how long patients on the study may survive, which could impact the timing of the release of topline data.

For more information about Berubicin clinical trial, visit clinicaltrials.gov and reference identifier NCT04762069.

Summary of Financial Results for the Full Year 2023

The net loss for the year ended December 31, 2023 was approximately $18.9 million compared to approximately $15.3 million for the comparable period in 2022. The change in net loss is primarily attributable to increased research and development costs.

The Company reported research and development expenses of $14.1 million for the year ended December 31, 2023 compared to approximately $9.3 million for the comparable period in 2022. The increase in research and development expenses during the period were mainly attributed to the timing of research organization (CRO) expenses and patient treatment costs related to continued progress with our clinical trial for Berubicin.

General and administrative expenses were approximately $4.8 million for the year ended December 31, 2023 compared to approximately $6.0 million for the comparable period in 2022. This change is primarily attributable to a decrease of approximately $792,000 in professional expenses, $488,000 in employee compensation, $141,000 in stock-based compensation and $92,000 in insurance expenses. These changes were offset by increases of approximately $145,000 in travel expenses, board of director compensation of $96,000, advertising and marketing of $68,000 and other general and administrative expenses of $7,000.

As of December 31, 2023, the Company had cash of approximately $0.5 million. Subsequent to the end of 2023, the Company closed a $4.0 million public offering with participation from healthcare-focused institutional investors, retail investors, and certain officers and directors of the Company. Management anticipates that its cash on hand as of December 31, 2023, combined with capital raised subsequent to December 31, 2023, is sufficient to fund its planned operations into but not beyond the latter half of the second quarter of 2024.

About Berubicin

Berubicin is the Company’s novel anthracycline and the first anthracycline to appear to cross the blood-brain barrier, for the treatment of GBM, an aggressive and incurable form of brain cancer.

Berubicin is currently being evaluated in a potentially pivotal, multicenter, open-label, randomized controlled study in adult patients with recurrent GBM (WHO Grade IV) after failure of standard first-line therapy and compared to Lomustine. The study has enrolled 252 patients across 46 clinical trial sites in the U.S., Italy, France, Spain, and Switzerland. The primary endpoint of the study is Overall Survival (OS), a rigorous endpoint the FDA has recognized as the basis for approval of oncology drugs when a statistically significant improvement can be shown relative to a randomized control arm.

The FDA has granted CNS Pharmaceuticals Fast Track Designation for Berubicin which enables more frequent interactions with the agency for guidance on expediting the development and review process. Additionally, the Company has received Orphan Drug Designation from the FDA, which may provide seven years of marketing exclusivity upon approval of an NDA.