On October 3, 2023 Synlogic, Inc. (Nasdaq: SYBX), a clinical-stage biotechnology company advancing novel, oral, non-systemically absorbed biotherapeutics to transform the care of serious diseases, reported the closing of its previously announced underwritten public offering (Press release, Synlogic, OCT 3, 2023, View Source [SID1234635602]).

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The offering consisted of 7,394,363 shares of common stock (or pre-funded warrants to purchase common stock in lieu thereof) and accompanying common warrants to purchase up to 7,394,363 shares of common stock. The combined effective offering price to the public of each share of common stock (or pre-funded warrant) and accompanying warrant was $2.84. The accompanying warrants have an exercise price of $3.408 per share, will be exercisable immediately, and will expire five years from the initial exercise date. The aggregate gross proceeds to Synlogic from the public offering were approximately $21.0 million, prior to deducting underwriting discounts, commissions and other estimated offering expenses. Participants in the offering included new and existing investors. Chardan acted as sole book-running manager for the offering.

Synlogic anticipates existing cash and cash equivalents and the proceeds from this offering will be sufficient to fund planned operations into the first half of 2025.

The Securities and Exchange Commission ("SEC") declared effective a registration statement on Form S-1 relating to these securities on September 27, 2023. A final prospectus relating to this offering was filed with the SEC. The offering was made only by means of a prospectus. Copies of the prospectus relating to the offering may be obtained from Chardan Capital Markets, LLC, 17 State Street, Suite 2130, New York, New York 10004, at (646) 465-9000, or by email at [email protected]. Investors may also obtain these documents at no cost by visiting the SEC’s website at View Source

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 October 3, 2023 Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that harness the power of the tumor microenvironment to overcome tumor immune evasion and drug resistance, reported clinical updates from its dose escalation portion of the Phase 1/2 study of NT219, a first in class dual inhibitor of Insulin receptor substrate (IRS) 1/2 and Signal Transducer and Activator of Transcription 3 (STAT3) and provides its outlook for planning the next clinical development steps with NT219 for second-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head & Neck (R/M SCCHN) (Press release, Purple Biotech, OCT 3, 2023, View Source [SID1234635601]).

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The Phase 1/2 study (NCT04474470), an open-label, dose escalation and expansion study is designed to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of NT219 as a monotherapy and in combination with Erbitux (cetuximab), in patients with R/M SCCHN, or with advanced colorectal cancer. Forty-nine patients were enrolled in five dose levels (3, 6, 12, 24 and 50 mg/kg); 27 in the monotherapy arm, and 22 in the combination therapy with cetuximab. Patients in both cohorts were dosed to the highest NT219 dose level of 50mg/kg. No dose-limiting toxicities (DLTs) were reported in either cohort and NT219 was well tolerated as a monotherapy and in combination with cetuximab.

A dose-dependent increase in drug exposure of NT219 was reported. The exposure achieved at the highest dose level of 50mg/kg was within the efficacy range of the human equivalent dose level as predicted from preclinical models. Inhibition of intra-tumoral IRS 1/2 and STAT3, NT219’s targets, was demonstrated in patients’ biopsies.

Among the four R/M SCCHN patients dosed at 50mg/kg of NT219 in combination with cetuximab, that were evaluable for efficacy, two patients demonstrated confirmed partial response by response evaluation criteria in solid tumors (RECIST) 1.1. Other results from the Phase 1/2 study will be provided at one of the upcoming medical conferences.

"We believe these results are very encouraging given the low response rate to cetuximab as monotherapy in recurrent/metastatic SCCHN patients in the second/third line," said Ari Rozenberg, M.D, University of Chicago and study Investigator. "While still early, we are excited to see responders at the highest NT219 dose level where we expected the appropriate exposure to be attained, along with evidence of on target treatment effect in patients’ biopsies. I look forward to continuing investigating NT219 and seeing more data in this disease setting with urgent need for improved therapies."

Treatment options for patients who had progressed following treatment with immunotherapy in first line R/M SCCHN are limited, with mostly cetuximab and chemotherapy currently available. The Company is in the process of designing a Phase 2 study of NT219 in combination with cetuximab in 2L R/M SCCHN. Such a study may evaluate NT219 in combination with cetuximab with or without standard of care chemotherapy following progression after immunotherapy in first line treatment.

Gil Efron, Purple Biotech CEO, added, "I am very satisfied with the observed activity of NT219 in recurrent and/or metastatic SCCHN patients. Due to the dire unmet need in this difficult to treat population, we believe that extending these early results through a robust proof of concept study would be meaningful for patients and for Purple Biotech and may lead us to next development steps. We will continue exploring higher dose optimization while designing our next study. We believe that the good tolerability of NT219 in combination with cetuximab can position this combination as a strong candidate to combine with other agents in 2L SCCHN and to achieve better survival for patients. Additionally, as demonstrated by our preclinical data, we believe that this data could potentially pave the way for development of NT219 in combination with EGFR inhibitors or other agents such as a-PD1 and KRAS inhibitors, potentially unlocking the full potential of NT219."

On October 3, 2023 Biodexa Pharmaceuticals PLC, (Nasdaq: BDRX), a clinical stage biopharmaceutical company developing a pipeline of products aimed at primary and metastatic cancers of the brain, reported that it has completed recruitment into cohort A of its ongoing Phase 1 study of MTX110 (also known as MAGIC-G1 study)(NCT 05324501) in patients with recurrent glioblastoma (rGBM) (Press release, Biodexa Pharmaceuticals, OCT 3, 2023, View Source [SID1234635600]).

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MAGIC-G1 is an open-label, dose escalation study designed to assess the feasibility and safety of intermittent infusions of MTX110 administered by convection enhanced delivery (CED) via implanted refillable pump and catheter. The study aims to recruit two cohorts (A and B), with a minimum of four patients in each; while patients in both cohorts receive MTX110 via intermittent repeated CED infusions, patients in the B cohort will be allowed CED catheter repositioning upon first in-study clinical and/or radiographic confirmed progression.

Following review by the Data Safety Monitoring Board (DSMB), the dose was escalated to 90µM after the first patient in cochort A and, because there have been no dose-limiting toxicities, recruitment into this cohort has concluded with the minimum of four patients. Patient 1 received 13 treatment cycles over 19 weeks of study treatment period, whereas patient 2 received 10 cycles over 13 weeks of study treatment period; patient 3 has, to date, received five cycles of treatment. The fourth patient underwent surgery yesterday and will receive their first cyle of treatment imminently.

Enrolment in cohort B will commence upon approval by the study DSMB, which is anticipated to be received towards the end of October 2023.

In addition, the Company is planning to add two more investigational centres into the study with activation expected in December 2023 and January 2024, respectively.

Commenting, Dr Dmitry Zamoryakhin, MD, MBA, CSO of Biodexa, said: "We are delighted to have concluded the recruitment of cohort A with the minimum number of patients based on the absence of drug-related adverse events. Cohort B of the study will provide a unique opportunity of continuous CED treatment after in-study tumour progression, which will be the first of its kind."

About Glioblastoma ("GB")

GB is the most common and devastating primary malignant brain tumour in adults encompassing 14.3% of all primary brain and central nervous system neoplasms(1). With an incidence of approximately 3.2 per 100,000 population in the USA, approximately 12,300 people in the USA will be diagnosed with GB per annum. Standard of care for treatment of GB is typically maximal surgical resection followed by radiotherapy plus concomitant and maintenance temozolomide chemotherapy with or without the Optune device. Notwithstanding, the multidisciplinary approach, almost all patients experience tumour progression with nearly universal mortality. The median survival from initial diagnosis is less than 21 months(2).

Currently, no standard of care is established for rGB.

Sources:
(1) Low JT, Ostrom QT, Cioffi G, Neff C, Waite KA, Kruchko C, Barnholtz-Sloan JS. Primary brain and other central nervous system tumors in the United States (2014-2018): A summary of the CBTRUS statistical report for clinicians. Neurooncol Pract. 2022 Feb 22;9(3):165-182. doi: 10.1093/nop/npac015. PMID: 35601966; PMCID: PMC9113389.
(2) Stupp R, Taillibert S, Kanner AA, et al. Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial. JAMA : the journal of the American Medical Association. 2015;314(23):2535-2543.
Chinot OL, Wick W, Mason W, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):709-722.

About MTX110

MTX110 is a water-soluble form of panobinostat free base, achieved through complexation with hydroxypropyl-β-cyclodextrin (HPBCD), that enables convection-enhanced delivery (CED) at potentially chemotherapeutic doses directly to the site of the tumour. Panobinostat is a hydroxamic acid and acts as a non-selective histone deacetylase inhibitor (pan-HDAC inhibitor). The currently available oral formulation of panobinostat lactate (Farydak) is not suitable for treatment of brain cancers owing to poor blood-brain barrier penetration and inadequate brain drug concentrations. Based on favourable translational science data, MTX110 is being evaluated clinically as a treatment for recurrent glioblastoma (NCT05324501), paediatric DMG (NCT04264143) and recurrent medulloblastoma (NCT04315064). MTX110 is delivered directly into and around the patient’s tumour via a catheter system (e.g. CED or fourth ventricle infusions) to bypass the blood-brain barrier. This technique exposes the tumour to very high drug concentrations while simultaneously minimising systemic drug levels and the potential for toxicity and other side effects. Panobinostat has demonstrated high potency against DIPG and GBM tumour cells in in vitro and in vivo models, and in a key study it was the most promising of 83 anticancer agents tested in 14 patient-derived DIPG cell lines (Grasso et al, 2015. Nature Medicine 21(6), 555-559).

On October 3, 2023 Kineta, Inc. (Nasdaq: KA), a clinical-stage biotechnology company focused on the development of novel immunotherapies in oncology that address cancer immune resistance, reported an update on its ongoing Phase 1/2 clinical trial evaluating KVA12123 in patients with advanced solid tumors (Press release, Kineta, OCT 3, 2023, View Source;utm_medium=rss&utm_campaign=kineta-announces-positive-kva12123-monotherapy-safety-and-biomarker-data-from-its-ongoing-phase-1-2-vista-101-clinical-trial [SID1234635598]). KVA12123, Kineta’s immuno-oncology drug targeting VISTA, cleared the first three monotherapy dose levels and was well tolerated with no dose limiting toxicities (DLT) or cytokine related adverse events observed. Additionally, KVA12123 exhibited a greater than dose-proportional pharmacokinetic profile achieving greater than 90% VISTA receptor occupancy (RO) across patients in the 30 mg dosing cohort.

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"We are very pleased with the progress of our Phase 1/2 clinical trial, showing very compelling initial safety and pharmacokinetic data for KVA12123, which we believe significantly de-risks VISTA as a novel drug target," said Shawn Iadonato, Ph.D., Chief Executive Officer of Kineta. "We appreciate the patients and healthcare providers that are participating in this important study, and we look forward to further evaluating KVA12123’s potential for treating patients with advanced solid tumors."

The VISTA-101 trial (NCT05708950) enrolled 11 patients with advanced solid tumors in the first three monotherapy dose-escalation cohorts, where subjects received either 3, 10 or 30 mg of KVA12123 by intravenous (IV) infusion every two weeks. Primary objectives of the Phase 1/2 study are to evaluate the safety and tolerability of KVA12123 and to determine the recommended Phase 2 dose (RP2D). Patients enrolled in the study were heavily pretreated with multiple prior lines of therapy including chemotherapy, radiation, and immunotherapy.

Safety Profile
In the first three monotherapy cohorts, KVA12123 was well tolerated at all doses and no DLTs were observed. Furthermore, as KVA12123 was engineered to mitigate adverse events associated with cytokine release syndrome (CRS), the study is closely monitoring proinflammatory cytokines that are associated with CRS (IL-6 and TNFα) in the Phase 1 portion of the study. No evidence of CRS or proinflammatory cytokine induction have been observed at any dose level with KVA12123 in the initial cohorts.

Pharmacokinetics and Receptor Occupancy
To guide the RP2D decision, Kineta developed a proprietary assay to evaluate VISTA RO on immune cells from patients treated with KVA12123. Greater than 90% VISTA RO was achieved at the 30 mg dose. Furthermore, pharmacokinetic analyses demonstrated a greater than dose-proportional increase in drug exposure across all evaluated doses, consistent with target-mediated drug disposition at lower doses.

"We are thrilled to see greater than 90% VISTA receptor occupancy in patients treated with 30 mg dose. This indicates that we can saturate the target without dose limiting toxicities and are close to achieving an optimal dose for KVA12123," said Thierry Guillaudeux, Ph.D., Chief Scientific Officer of Kineta. "We believe that KVA12123 has the potential to become an important new immunotherapy for the many patients with cancer in need of new therapeutic options."

Competitive therapies targeting VISTA have demonstrated either poor monotherapy anti-tumor activity in preclinical models or induction of CRS in human clinical trials. Through the combination of unique epitope binding and an optimized IgG1 Fc region, KVA12123 demonstrates strong monotherapy tumor growth inhibition in preclinical models without evidence of CRS in clinical trial participants. KVA12123 effectively de-risks the VISTA target and provides a novel approach to address immune suppression in the TME with a mechanism of action that is differentiated and complementary with T cell focused therapies. KVA12123 may be an effective immunotherapy for many types of cancer including non-small cell lung (NSCLC), colorectal, renal cell carcinoma, head and neck, and ovarian cancer.

The company will continue escalating monotherapy dose cohorts of KVA12123 in Part A and initiate Part B of the study to evaluate KVA12123 in combination with pembrolizumab. Initial monotherapy efficacy data are anticipated in Q4 2023 and will be presented, along with safety data, at an upcoming medical conference.

On October 3, 2023 Invitae (NYSE: NVTA), a leading medical genetics company, reported it gained FDA market authorization for its Common Hereditary Cancers Panel (Press release, Invitae, OCT 3, 2023, View Source [SID1234635597]). This represents the first broad panel that is used to identify germline variants associated with hereditary cancer to gain market authorization from the FDA. The company believes that this is a strong vote of confidence in its Common Hereditary Cancers Panel, which has the potential to benefit patients, providers and payers.

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Through this application, Invitae was able to establish a new category of device based on its testing technology and methodology which provides potential marketing differentiation and opportunities for its largest testing category. In 2021, the company submitted a de novo application using the Common Hereditary Cancers Panel as an example of a methods-based approach to validation. The FDA worked closely with Invitae to review the test and its supporting data, which led to this authorization being granted on September 29, 2023.

"This is incredibly exciting news for Invitae. We were able to demonstrate that the way the technology works can be well characterized based on variant type and genomic context and is consistent across genes," said Robert Nussbaum, M.D., chief medical officer at Invitae. "The fact that we were able to do this is a testament to Invitae’s quality and rigorous validation process that met the agency’s standards."

About the Common Hereditary Cancers Panel

The Invitae Common Hereditary Cancers Panel is an in vitro diagnostic test focused on 47 genes already known to contain tens of thousands of genetic variants that increase risk of developing certain cancers. Hereditary cancer testing represents the largest business line of Invitae’s testing portfolio, and multiple peer-reviewed studies1 published in recent years have demonstrated its clinical utility. That utility includes determining the potential risk for cancer, informing management and treatment of those with the disease and helping to prevent disease in those at increased risk. To learn more, visit our website.

Intended Use of the Market Authorization

The Invitae Common Hereditary Cancers Panel is a qualitative high throughput sequencing-based in vitro diagnostic test system intended for analysis of germline human genomic DNA extracted from whole blood for detection of substitutions, small insertion and deletion alterations and copy number variants (CNV) in a panel of targeted genes. This test system is intended to provide information for use by qualified health care professionals in accordance with professional guidelines, for hereditary cancer predisposition assessment and to aid in identifying hereditary genetic variants potentially associated with a diagnosed cancer. The test is not intended for cancer screening or prenatal testing. Results are intended to be interpreted within the context of additional laboratory results, family history and clinical findings. The test is a single-site assay performed at Invitae Corporation.