On February 14, 2024 TC BioPharm (Holdings) PLC ("TC BioPharm" or the "Company") (NASDAQ: TCBP) a clinical stage biotechnology company developing platform allogeneic gamma-delta T cell therapies for cancer and other indications, reported a shareholder update with a projected outlook for the current year (Press release, TC Biopharm, FEB 14, 2024, View Source [SID1234640101]).

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"The previous year was a time of significant operational achievement for TC BioPharm," said Bryan Kobel, Chief Executive Officer. "Despite strong headwinds throughout financial markets, we announced capital infusions of [approximately] $11.6 million while streamlining efficiencies, successfully dosing the final patient our ACHIEVE Study safety cohort and receiving FDA clearance of the Company’s investigational new drug (IND) application for a Phase 1B study in relapse/refractory Acute Myeloid Leukemia (AML). Additionally, we announced a new collaboration with Queen Mary University of London to expand TCB-008 into anti-fungal and anti-bacterial diseases, including non-dilutive funding to advance the project at lesser/lessened cost to the Company. Our team remains confident in TCB-008 as a therapeutic both as a monotherapy and in combination with other cell and immune system focused therapeutics, and looks forward to receiving interim data for the ACHIEVE trial in 2024. In March of 2023, we gave the investment community a roadmap of milestones we looked to complete in the subsequent 9 months of 2023, and it’s a great credit to the team that the Company was able to successfully achieve each of these milestones. We look forward/expect to continue this pattern of execution in 2024 and hitting our key milestones as laid out."

Recent Company Updates

● FDA clearance of investigational new drug (IND) application for a Phase 1B study in relapse/refractory Acute Myeloid Leukemia (AML)
● The Company streamlined efficiencies and reduced overhead on several fronts
● Formed a third-party manufacturing partnership in US with Excellos
● Entered into a collaboration agreement with Queen Mary University of London (QMUL) to expand the platform into non-oncology indications. The QMUL project received grant funding from The Impact Fund arm of QMUL, to research the therapeutic potential of gamma-delta T cells for the treatment of mucosal infections.
● Completed ACHIEVE Safety Cohort and received positive review from the Data Safety Monitoring Board (DSMB).

2024 Potential Milestones

● Interim data review for ACHIEVE trial studying TCB-008 in Acute Myeloid Leukemia
● Management is focused on leveraging existing strategic relationships in order to execute partnerships and or collaborations in combination with TCB-008.
● Platform expansion with Proof of Concept and preclinical work completed for its anti-fungal/anti-bacterial program
● Expected budget savings of approximately $11.6M after eliminating redundancies and asset prioritization efforts.

Filing of Preliminary Proxy Statement

On February 9, 2024 the Company filed a preliminary proxy statement with the Securities and Exchange Commission which included a proposal to obtain shareholder approval, in accordance with Nasdaq Marketplace Rule 5635(d), regarding the proposed sale, issuance, or potential issuance by the Company of Ordinary Shares or ADSs, in connection with certain non-public offerings, of the Ordinary Shares or ADSs (and/or securities convertible into or exercisable for Ordinary Shares or ADSs) equal to 20% or more outstanding immediately prior to the issuance of such securities at a price less than the lower of: (i) the closing price immediately preceding the signing of the binding agreement, or (ii) the average closing price of the ADSs for the five trading days immediately preceding the signing of the binding agreement for the transaction, subject to certain limitations. The Board of Directors of the Company has not yet determined the terms and conditions of any potential financing(s). This filing is not a registration statement and no shares have been issued or registered with the Securities and Exchange Commission (SEC). TC BioPharm has taken this step in light of converting from foreign filer status to a domestic filer status, and in order to comply with NASDAQ marketplace rules that are applicable to domestic filers.

Kobel continued, "In 2024, our goal is to make additional strides throughout our pipeline of differentiated gamma delta T cell therapies via a strategic and disciplined approach. Receiving clearance on our IND from the U.S. FDA of TCB-008 in Acute Myeloid Leukemia marks an important milestone in maximizing our lead therapeutics’ opportunity in the category of blood cancers that we believe it is ideally suited to address. Additionally, last week the Company filed a preliminary proxy statement relating to the Nasdaq stock exchange’s requirement of obtaining shareholder approval for the potential issuance of more than 20% of the shares outstanding. This relates to being positioned to effectively execute our business strategy over the coming 90 days, both in the M&A arena and access to capital, and is a function of timing as we shift from foreign filer status to domestic filer status for SEC reporting and NASDAQ compliance purposes."

On February 14, 2024 Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) ("Sonnet" or the "Company"), a clinical-stage biopharmaceutical company developing targeted immunotherapeutic drugs for cancer, reported its financial results for the three months ended December 31, 2023 and provided a business update (Press release, Sonnet BioTherapeutics, FEB 14, 2024, View Source [SID1234640100]).

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"This last quarter set the stage for an exciting year across Sonnet’s pipeline, highlighted by the progress of the combination study of SON-1010 and atezolizumab in platinum-resistant ovarian cancer (PROC), where we continue to expect safety data during the first half of 2024." commented Pankaj Mohan, Ph.D., Founder and CEO. "Additionally, enrollment of the Phase 1b portion of the SON-080 study in patients with CIPN is now finished. We believe this trial will yield important safety data that could help position the asset for a potential partnering opportunity in this indication, as well as in diabetic peripheral neuropathy (DPN), both indications of high unmet medical need. On the operations side, we continue the work to optimize our cash usage and runway, including leveraging tax credits. From the sale of the New Jersey NOLs, we expect to receive net proceeds of $4.3 million, after deducting expected fees, during February 2024. Pending the completion of this sale, we believe it will extend the funding of our projected operations into the third calendar quarter of 2024. Taken together, we are pleased with the progress of our clinical programs and look forward to updating the market on our continued progress over the balance of 2024."

Fiscal Year 2024 First Quarter and Recent Corporate Updates

Sonnet provided the following corporate updates:

● On October 17, 2023, announced that interim data from the SB101 clinical trial of the company’s proprietary Fully Human Albumin Binding (FHAB) candidate, SON-1010 (IL12- FHAB), would be presented by Dr. Sant Chawla, a key opinion leader in the field of sarcoma research, at the Connective Tissue Oncology Society Annual Meeting 2023, held November 1-4, 2023, in Dublin, Ireland.
● On October 25, 2023, announced the pricing of an underwritten public offering of 2,843,750 shares of common stock (or pre-funded warrants to purchase shares of common stock in lieu of shares of common stock) and investor warrants to purchase up to an aggregate of 5,687,500 shares of common stock. Each share of common stock (or pre-funded warrant in lieu thereof) was sold together with two investor warrants at a combined offering price of $1.60, for total gross proceeds of approximately $4.55 million (final net proceeds were $3.9 million), before underwriting discounts and commissions and offering expenses payable by Sonnet.

● On December 21, 2023, announced the publication of extensive preclinical data on SON-1210 in Frontiers in Immunology. SON-1210, Sonnet’s lead proprietary bifunctional compound, combines the company’s FHAB construct with a novel single-chain Interleukin 12 (IL-12) and fully human Interleukin 15 (IL-15). The paper, entitled "SON-1210 – a novel bifunctional IL-12 / IL-15 fusion protein that improves cytokine half-life, targets tumors, and enhances therapeutic efficacy", demonstrated the robust binding affinity of SON-1210 to albumin and the anticipated in vitro activity and tumor model efficacy that might be expected from the body of research on native IL-12 and IL-15. In the B16F10 melanoma model, a single dose resulted in a marked reduction of tumor growth that was concomitant with increased IFNγ and augmented immune cell numbers and activity in the tumor microenvironment. Repeat doses in non-human primates displayed excellent safety and tolerability and were similarly accompanied by increased IFNγ levels.
● In December 2023, Sonnet received preliminary approval of its application to sell up to $4.8 million of its New Jersey state net operating losses (NOLs) through the Technology Business Tax Certificate Transfer Program. On January 24, 2024, the Company executed an agreement pursuant to the program whereby a buyer has agreed to purchase, and the Company agreed to sell, such NOLs. Sonnet expects to receive net proceeds of $4.3 million, after deducting expected fees, during February 2024. Pending the completion of the sale of the New Jersey NOLs, Sonnet believes it will extend the funding of its projected operations into the third calendar quarter of 2024.
● Also during December 2023, Sonnet received a $0.8 million net cash refund from the research and development tax incentive program in Australia.
● Safety was recently reviewed for the 2nd dose-escalation cohort in the SB221 Phase 1b combination study (NCT05756907) in patients with platinum-resistant ovarian cancer (PROC) and enrollment has begun in the 3rd cohort. Enrollment continues in the final dose-escalation cohort with SON-1010 monotherapy in SB101 (NCT05352750) cancer patients. Safety updates for both studies are expected during the first half of 2024.
● Enrollment has finished in the Phase 1b safety portion of the SB211 study of SON-080 (NCT05435742) in patients with persistent CIPN. A safety update from this trial is expected during the first quarter of 2024.
● Regarding the agreement with Janssen, the parties have completed two combination studies in a prostate tumor model. A review of the resulting data remains ongoing.

"As our pipeline continues to advance, we remain focused on areas for further operating expense reductions." said Jay Cross, CFO. "Furthermore, we are diligently working to expand on our business development accomplishments, in an otherwise highly competitive environment."

FY 2024 First Quarter Ended December 31, 2023, Financial Results

● As of December 31, 2023, Sonnet had $3.0 million cash on hand and no debt.
● Research and development expenses were $0.6 million for the three months ended December 31, 2023, compared to $3.7 million for the three months ended December 31, 2022. The decrease of $3.1 million was primarily due to the cancellation of accrued but unpaid bonuses that had been awarded for fiscal years 2022 and 2023 in the amount of $1.0 million, as well as due to cost saving initiatives, as we are managing expenses for liquidity purposes and are tightening our focus on the research and development projects we have assessed to have the greatest near-term potential. In addition to transitioning product development activities to cost advantaged locations such as India and Australia, we have reduced expenditures on tertiary programs and suspended antiviral development related to SON-1010.
● General and administrative expenses were $0.7 million for the three months ended December 31, 2023, compared to $1.9 million for the three months ended December 31, 2022. The decrease of $1.3 million relates primarily to the cancellation of accrued but unpaid bonuses that had been awarded for fiscal years 2022 and 2023 in the amount of $0.9 million, and due to cost saving initiatives, as we are managing expenses for liquidity purposes.

On February 14, 2024 Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company working to achieve regulatory approval for the first ophthalmic formulation of bevacizumab for the treatment of retinal diseases, reported financial results for first quarter fiscal year 2024 and provided a corporate update (Press release, Outlook Therapeutics, FEB 14, 2024, View Source [SID1234640099]).

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"We are proud of the recent progress our team has made. In January 2024, we received confirmation that the FDA has reviewed and agreed upon the NORSE EIGHT trial protocol pursuant to the SPA they approved. We also reached agreement that if the NORSE EIGHT trial is successful, it would satisfy the FDA’s requirement for a second adequate and well-controlled clinical trial to address fully the clinical deficiency identified in the CRL. Importantly, the first subject was enrolled in NORSE EIGHT in January 2024," commented Russell Trenary, President and Chief Executive Officer. "In addition, through a Type A meeting and additional interactions, we have identified the approaches needed to resolve the CMC comments in the CRL. We are working to address the open items and expect to resolve these comments prior to the expected completion of NORSE EIGHT. Finally, we have entered into purchase agreements for a financing of up to $172 million, subject to shareholder approval, to support our regulatory efforts and launch preparations."

Upcoming Anticipated Milestones

Closing of private placement financing in March 2024, subject to receipt of stockholder approval and other closing conditions;
MAA decision date in the EU for ONS-5010 targeted for first half of 2024;
Completion of NORSE EIGHT in the United States anticipated in 2024; and
Resubmission of the ONS-5010 BLA expected by the end of calendar year 2024.
ONS-5010 / LYTENAVA (bevacizumab-vikg) Regulatory Update

As previously announced, following a Type A meeting with the FDA in October 2023, the FDA informed Outlook Therapeutics that it can conduct a non-inferiority study evaluating ONS-5010 versus ranibizumab in a 3-month study of treatment naïve patients with a primary efficacy endpoint at 2 months (NORSE EIGHT). In January 2024, Outlook Therapeutics announced that it received written agreement on the NORSE EIGHT trial protocol from the FDA under a SPA for NORSE EIGHT. The SPA confirms that if the NORSE EIGHT trial is successful, it would satisfy the FDA’s requirement for a second adequate and well-controlled clinical trial to fully address the clinical deficiency identified in the Complete Response Letter (CRL). In addition, through a Type A meeting and additional interactions, Outlook Therapeutics has identified the approaches needed to resolve the Chemistry, Manufacturing and Controls (CMC) comments in the CRL. Outlook Therapeutics is working to address the open CMC items in the CRL and expects to resolve these comments prior to the expected completion of NORSE EIGHT.

NORSE EIGHT is a randomized, controlled, parallel-group, masked, non-inferiority study of approximately 400 newly diagnosed, wet AMD subjects randomized in a 1:1 ratio to receive 1.25 mg ONS-5010 or 0.5 mg ranibizumab intravitreal injections. Subjects will receive injections at Day 0 (randomization), Week 4, and Week 8 visits. The primary endpoint will be mean change in BCVA from baseline to week 8. Outlook Therapeutics expects NORSE EIGHT topline results and resubmission of the ONS-5010 BLA by the end of calendar year 2024.

Additionally, the formal review process of the ONS-5010 MAA by the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) is underway with an estimated decision date expected in the first half of 2024. In addition to pursuing potential strategic partnering opportunities in the EU and other regions, Outlook Therapeutics is also exploring potential expanded relationships with Cencora (formerly AmerisourceBergen) to support the launch of ONS-5010 in international markets.

If approved, ONS-5010 / LYTENAVA (bevacizumab-vikg) would be the first approved ophthalmic formulation of bevacizumab in the U.S. or EU.

Financial Highlights for the Fiscal First Quarter Ended December 31, 2023

For the fiscal first quarter ended December 31, 2023, Outlook Therapeutics reported a net loss attributable to common stockholders of $11.2 million, or $0.04 per basic and diluted share, compared to a net loss attributable to common stockholders of $18.7 million, or $0.08 per basic and diluted share, for the same period last year.

In January 2024, the Company announced that it has entered into definitive securities purchase agreements with certain institutional and accredited investors to purchase shares of common stock and accompanying warrants in private placements, the closing of which is conditioned upon stockholder approval of the transactions and certain other corporate actions, expected in the first quarter of 2024. The private placements are expected to provide up to $65 million in gross proceeds at closing, before deducting placement agent fees and offering expenses. In addition, Outlook Therapeutics will have the potential to receive additional gross proceeds of up to $107 million upon the full cash exercise of the warrants being issued in the private placements, before deducting placement agent fees and offering expenses. The warrants include a feature that allows Outlook Therapeutics to require cash exercise if certain stock price and milestone conditions are met.

At December 31, 2023, Outlook Therapeutics had cash and cash equivalents of $10.4 million. Assuming closing of the private placements as planned (subject to closing conditions) and full cash exercise of the related warrants, the proceeds from the private placements are expected to support business operations, complete the execution of NORSE EIGHT, resubmit the ONS-5010 BLA and, if approved, support the commercial launch of ONS-5010.

About ONS-5010 / LYTENAVA (bevacizumab-vikg)

ONS-5010 is an investigational ophthalmic formulation of bevacizumab under development as an intravitreal injection for the treatment of wet AMD and other retinal diseases. Because no FDA-approved ophthalmic formulations of bevacizumab are available currently, clinicians wishing to treat retinal patients with bevacizumab have had to use unapproved repackaged IV bevacizumab provided by compounding pharmacies—products that have known risks of contamination and inconsistent potency and availability. If approved, ONS-5010 would provide an FDA-approved option for physicians that currently prescribe unapproved repackaged oncologic IV bevacizumab from compounding pharmacies for the treatment of wet AMD.

Bevacizumab-vikg is a recombinant humanized monoclonal antibody (mAb) that selectively binds with high affinity to all isoforms of human vascular endothelial growth factor (VEGF) and neutralizes VEGF’s biologic activity through a steric blocking of the binding of VEGF to its receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) on the surface of endothelial cells. Following intravitreal injection, the binding of bevacizumab-vikg to VEGF prevents the interaction of VEGF with its receptors on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation in the retina.

On February 14, 2024 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported that management will participate in a fireside chat at the Citi 2024 Virtual Oncology Leadership Summit on Wednesday, February 21, 2024, at 3:00 p.m. ET (Press release, ORIC Pharmaceuticals, FEB 14, 2024, View Source [SID1234640098]).

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A live webcast of the discussion will be available through the investor section of the company’s website at www.oricpharma.com. A replay of the webcast will be available for 90 days following each event.

On February 14, 2024 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), a clinical-stage immunotherapeutics company focused on oncology, reported the expansion of enrollment for the anal cancer cohort of the GOBLET study evaluating pelareorep in combination with atezolizumab (Tecentriq) in patients with second-line or later unresectable squamous cell carcinoma of the anal canal (SCCA) (Press release, Oncolytics Biotech, FEB 14, 2024, View Source [SID1234640097]). The study was expanded based on positive data from Stage 1 of the study, presented at the 2nd International Multidisciplinary Anal Cancer Conference (IMACC) in November 2023 (link to the PR, link to the poster).

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"These exciting clinical data, which exceed the Simon two-stage success criteria, provide strong support to expand the evaluation of pelareorep in patients with advanced anal cancer. The results reported at IMACC 2023 showed that the combination of pelareorep and atezolizumab provided a 37.5% objective response rate, including one patient with a long-lasting complete response, and good overall tolerability. These data represent a meaningful contrast to recent clinical trial results which show that patients with second-line or later anal carcinoma treated with checkpoint inhibitor therapy experienced response rates of 10-14%1-3," said Dr. Matt Coffey, President and Chief Executive Officer of Oncolytics."

"We begin the Stage 2 expansion with substantial optimism for patients and the potential of pelareorep, especially considering the initial efficacy signal observed for pelareorep-based therapy in pancreatic cancer. There is currently no established standard therapy for patients with anal carcinoma who have failed first-line treatment. Continued positive results could potentially expand the opportunity for pelareorep beyond the lead indications of breast cancer and pancreatic cancer and open the door to a rapid regulatory pathway in this rare and significantly under-served patient population," continued Dr. Coffey.

Dirk Arnold, M.D., Ph.D., Director of Asklepios Tumorzentrum Hamburg, and primary investigator of the GOBLET trial, commented, "One of the most difficult challenges in my practice is the limited number of treatment options that are available for patients with advanced anal cancer who have progressed on first-line therapy. I am enthusiastic about the expansion of this cohort because it will enable the continued evaluation of the pelareorep/atezolizumab combination and could provide important confirmatory data that may lead to better treatment options for patients with this late-stage disease."

"We look forward to building on the oncology community’s enthusiastic reception of the IMACC 2023 data by expanding enrollment in the anal carcinoma cohort and incorporating additional sites into the study," commented Thomas Heineman, M.D., Ph.D., Chief Medical Officer at Oncolytics. "Careful consideration of recently published clinical trial results indicates that a modest expansion of fewer than 20 patients will be sufficient to solidify the efficacy signal we have observed to date and lay the groundwork for a potential future registrational study in this population. We look forward to continuing our excellent collaboration with the clinical sites and investigators at AIO and hope to report additional results in 2025."

About GOBLET
The GOBLET (Gastrointestinal tumOrs exploring the treatment comBinations with the oncolytic reovirus peLarEorep and anTi-PD-L1) study is a phase 1/2 multiple indication study in advanced or metastatic gastrointestinal tumors. The study is being conducted at 12 centers in Germany and is being managed by AIO-Studien-gGmbH. The co-primary endpoints of the study are objective response rate (ORR) assessed at week 16 and safety. Key secondary and exploratory endpoints include additional efficacy assessments and evaluation of potential biomarkers (T cell clonality and CEACAM6). The study employs a Simon two-stage design with Stage 1 comprising four treatment groups:

1.Pelareorep in combination with atezolizumab, gemcitabine, and nab-paclitaxel in 1st line advanced/metastatic pancreatic cancer patients;

2.Pelareorep in combination with atezolizumab in 1st line MSI (microsatellite instability)-high metastatic colorectal cancer patients;

3.Pelareorep in combination with atezolizumab and TAS-102 in 3rd line metastatic colorectal cancer patients; and

4.Pelareorep in combination with atezolizumab in 2nd line advanced and unresectable anal cancer patients.

Any cohort meeting pre-specified efficacy criteria in Stage 1 may be advanced to Stage 2 and enroll additional patients.