On February 13, 2023 MacroGenics Inc, a biopharmaceutical company focused on developing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported preliminary safety and anti-tumor activity data from the dose expansion phase of the Company’s ongoing Phase 1 clinical trial of lorigerlimab, a bispecific, tetravalent PD-1 × CTLA-4 DART molecule (Press release, MacroGenics, FEB 13, 2023, View Source [SID1234636050]). This investigational molecule was designed to block PD-1 with enhanced CTLA-4 blockade on dual PD-1/CTLA-4-expressing cells, such as tumor-infiltrating lymphocytes (TILs), while maintaining maximal PD-1 blockade on all PD-1-expressing cells. The preliminary data is being presented in a poster titled "Lorigerlimab, a Bispecific PD-1 × CTLA-4 DART Molecule in Patients with Metastatic Castration-Resistant Prostate Cancer: A Phase 1 Expansion Cohort" (Poster #155) at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary (ASCO-GU) Cancers Symposium taking place February 16-18, 2023, in San Francisco, CA.

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Cohort Expansion Results Update

The ASCO (Free ASCO Whitepaper)-GU abstract included data as of September 10, 2022; updated data as of a December 12, 2022 cut-off are included below and will be presented at ASCO (Free ASCO Whitepaper)-GU.

As of the December 12, 2022 data cut-off, 118 patients with mCRPC, melanoma, non-small cell lung cancer or microsatellite-stable colorectal cancer were enrolled in the cohort expansion phase of the lorigerlimab Phase 1 study at the dose of 6.0 mg/kg, administered intravenously every three weeks (Q3W). Confirmed objective responses were observed across the histology-specific cohorts; preliminary efficacy results for mCRPC are presented in the poster and below.

Preliminary Safety Results

The safety analysis is based on 127 patients who received lorigerlimab at a dose of 6 mg/kg Q3W, including 118 enrolled in the four dose expansion cohorts plus nine patients from dose escalation. Median exposure was 14.4 weeks (range: 1.9 – 100.1 weeks) with a median of four infusions administered per patient. Twenty-four patients remained on lorigerlimab as of the December 12, 2022 data cut-off; 103 discontinued for the following reasons: progressive disease (PD) (n=66), adverse events (AE) (n=31), patient/physician decision (n=5), or death due to PD (n=1).

The results demonstrated a manageable overall safety profile. Treatment-related AEs (TRAEs) occurred in 86.6% of patients, with the most common among them (≥15%) being fatigue, rash, pruritus, hypothyroidism, and pyrexia. Rates of grade ≥3 TRAEs and immune-related AEs were 34.6% and 7.9%, respectively. AEs resulted in treatment discontinuation in 24.4% of patients. There were no fatal AEs related to lorigerlimab.

Preliminary Anti-tumor Activity in mCRPC Cohort

As of the December 12, 2022 data cut-off, 42 patients had been enrolled in the mCRPC expansion cohort. Patients had previously received a median of two prior therapies (range: 1 – 9) for advanced disease, with 35 patients (83.3%) having received docetaxel and 34 patients (81.0%) having received androgen receptor antagonist therapy. The median exposure to lorigerlimab was 19.2 weeks (range: 3.3 – 55.1 weeks), with a median of five infusions administered per patient.

A total of 35 patients with mCRPC had measurable soft tissue disease per RECIST v1.1 at study entry. Nine of the 35 patients (25.7%) achieved confirmed partial responses (cPR). The median duration of response for these nine patients was 4.6 months (range: 2.8 – 8.6+ months), with four patients remaining on lorigerlimab as of data cut-off. Among the other five patients who had achieved cPR, four discontinued due to unrelated adverse events, and one patient discontinued due to physician decision.

Reductions in PSA levels of ≥ 50% were observed in 12 of 42 patients (28.6%), and 9 of the 12 maintained PSA50 response ≥ 3 months. Nine of 42 patients (21.4%), including the nine who achieved cPR, had reductions in their PSA levels of ≥ 90% as of the data cut-off.

"To date, checkpoint inhibition has not fared well in the treatment of patients with late-stage mCRPC. Previously, anti-CTLA-4 therapy, whether alone or in combination with an anti-PD-1 agent, resulted in increased risk for immune-related toxicity with very modest anti-tumor activity," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "We designed lorigerlimab to have preferential blockade on dual PD-1/CTLA-4-expressing cells such as TILs, which are most abundant in the tumor microenvironment. As part of this study, biomarker analyses indicated that lorigerlimab was shown to induce T-cell activation as evidenced by an increased frequency of circulating Ki67+ and ICOS+ T cells. We believe we are seeing the benefit of lorigerlimab’s design and are very encouraged by this latest data set from our ongoing Phase 1 study. Looking forward, we plan to initiate a Phase 2 study of lorigerlimab in patients with mCRPC later this year and anticipate providing an update on the proposed study later this quarter."

ASCO-GU Poster Presentation

MacroGenics’ lorigerlimab poster presentation will be available for on-demand viewing on the ASCO (Free ASCO Whitepaper)-GU website and on the "Events & Presentations" page on MacroGenics’ website at View Source

About Lorigerlimab

Lorigerlimab (previously known as MGD019) is an investigational, bispecific IgG4-based, Fc-bearing DART molecule that was designed to enhance blockade on PD-1 and CTLA-4 dual-expressing, tumor-infiltrating lymphocytes, while maintaining maximal PD-1 blockade on all circulating PD-1-expressing cells. In addition to the study described above and presented in the poster, MacroGenics is also evaluating the activity of lorigerlimab in combination with vobramitamab duocarmazine (previously known as MGC018, an investigational B7-H3-directed antibody-drug conjugate) in a study in patients with advanced solid tumors.

On February 13, 2023 Biocity Biopharma reported that the U.S. Food and Drug Administration (FDA) has granted the company’s Investigational New Drug (IND) application for the investigational drug BC3195 (CDH3 ADC) (Press release, Biocity Biopharmaceutics, FEB 13, 2023, View Source [SID1234633307]). The approval enables Biocity Biopharma to conduct the phase 1 study of BC3195 in Patients with Locally Advanced or Metastatic Solid Tumors in the United States. This is the second US IND approval in the past few months, which is another important milestone for Biocity Biopharma in its effort to extend product development globally.

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BC3195 is a novel ADC targeting CDH3/P-cadherin, a calcium-dependent cell-cell adhesion glycoprotein expressed in a variety of malignancies, including lung, breast, gastric, ovarian, colorectal, and pancreatic cancers.
CDH3 is highly expressed in malignant tumors with low or no expression in normal tissues, which makes it an ideal target to develop anticancer treatment, particularly for the development of ADCs.
In preclinical study, BC3195 binds to cell surface CDH3 and is efficiently internalized. In different animal models, BC3195 demonstrated good safety profile and strong antitumor activities with tumor growth inhibition reaching up to 100%.
BC3195 a first-in-class new generation ADC designed with a clinically validated linker and payload (MMAE) that has bystander effect.
Currently, BC3195 is the only ADC targeting CDH3 in clinical development globally.Biocity Biopharma believes that BC3195 may hold the promise of becoming a novel treatment for patients with advanced cancers where high unmet medical needs still exist.

On March 13, 2023 IMV Inc. (Nasdaq: IMV; TSX: IMV) ("IMV" or the "Company"), a clinical-stage biopharmaceutical company developing a portfolio of immune-educating therapies based on its novel DPX platform to treat solid and hematologic cancers, reported positive preliminary data from the VITALIZE Phase 2B trial evaluating its lead DPX product, maveropepimut-S ("MVP-S"), in combination with pembrolizumab in patients with relapsed, refractory Diffuse Large B Cell Lymphoma ("r/r DLBCL") (Press release, IMV, FEB 13, 2023, View Source [SID1234628586]).

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Key initial findings from the ongoing VITALIZE trial:

8 Patients with an ECOG1 score of 0-1 have been enrolled in arm 1 of the study. Of these, 6 have so far been evaluable for efficacy;
Of these 6 evaluable patients, 3 patients showed confirmed complete responses, 1 patient was assessed with stable disease as best response and 2 patients were assessed with progressive disease as best response; and
2 patients with poor level of baseline functionality (ECOG ≥ 2) failed to stay on study through to the first scan and therefore could not be evaluated.
Overall Response Rate ("ORR") will be communicated when the totality of stage one data are available for definitive assessment.

"VITALIZE is our most advanced and rigorous trial to date, and we are encouraged by the way the data for MVP-S are trending. This is the most refractory population of patients we have treated so far, and to show complete, confirmed clinical responses is notable. These positive initial results, combined with the accelerating recruitment of the AVALON study in platinum resistant ovarian cancer add, we believe, to the growing industry enthusiasm about the potential for MVP-S in multiple tumor settings," said Andrew Hall, CEO of IMV.

About the VITALIZE Study

The VITALIZE Phase 2B trial is a randomized, parallel group, Simon two-stage study designed to assess IMV’s lead candidate, MVP-S, in combination with pembrolizumab with (arm 1) or without (arm 2) cyclophosphamide. Across the arms of this study, the combination will be evaluated in up to 30 patients in stage one (two arms of 15) with the option to expand to up to a total of 102 subjects in stage two with r/r DLBCL who have received at least two prior lines of systemic therapy and who are ineligible or have failed autologous stem cell transplant (ASCT) or CAR-T therapy.

About the AVALON study

The AVALON study is an open label, company-sponsored phase 2b, single arm trial evaluating the efficacy and safety of MVP-S and intermittent low-dose cyclophosphamide (CPA) in patients with platinum-resistant ovarian cancer. The study is a Simon two-stage design where up to 41 subjects will be evaluated in stage one, with the option to expand to up to a total of 73 patients in stage two. Patients participating in the trial will receive two doses of subcutaneous MVP-S once every three weeks, followed by an MVP-S dose once every eight weeks, plus low-dose oral CPA on a repeating cycle of one week on/one week off.

On February 13, 2023 Hillstream BioPharma, Inc. (Nasdaq: HILS) ("Hillstream" or the "Company"), a biotechnology company developing therapeutic candidates targeting drug resistant and devastating cancers using ferroptosis, an emerging new anti-cancer mechanism resulting in iron mediated cell death, and immuno-oncology targeted novel biologics, reported signing an exclusive option agreement with Applied Biomedical Science Institute (ABSI) to license technology for HER2 and HER3 Conformational Domain Bridging Epitopes in human monoclonal antibodies to develop proprietary multi-format biologics (bi- and tri-specific antibodies, ADCs (antibody drug conjugates), CAR-T and CAR-NKs, in Quatramers and Quatrabodies) against drug resistant cancers including HER2-positive metastatic breast cancer, gastric cancer, lung cancer and ovarian cancer (Press release, Hillstream Biosciences, FEB 13, 2023, View Source [SID1234628150]).

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The ErbB family of cell surface proteins are some of the most well-known and validated oncology drug targets including ErbB2 or HER2 (human epidermal growth factor receptor) and Erb3 or HER3. The family of antibodies and biologics against HER2 starting with HERCEPTIN (trastuzumab) approved in 1998 for breast cancer, one of the first few anti-cancer antibodies, as well as PERJETA, KADCYLA and PHESGO totaled $8.4 billion in 2022 sales for Roche/Genentech. Antibodies against HER2 and HER3 bind to different domains of the extracellular portion of the proteins or epitopes with trastuzumab binding domain IV of HER2 primarily. HER2 is also one of the most utilized targeting antigens for antibody drug conjugates to treat HER2 positive cancers with two approved antibodies, Roche/Genentech’s PERJETA and Daiichi Sankyo/AstraZeneca’s ENHERTU.

The Applied Biomedical Science Institute has developed technology to target unique functional epitopes of the cancer targets HER2 and HER3. Monoclonal antibodies being developed at ABSI are unique from the currently approved anti-HER2 antibodies. ABSI has granted under an exclusive option agreement to Hillstream, certain of its proprietary technology which if converted to an exclusive license agreement, will allow Hillstream to develop HER2 and HER3 antibodies, including multi-specific and Quatramer- based therapeutics incorporating portions of the antibodies.

"We look forward to this unique opportunity to work with Dr. Smider and the Applied Biomedical Science Institute," said Randy Milby, CEO of Hillstream. "This agreement allows Hillstream to build our antibody platform to advance our immune-oncology biologic pipeline with HER2 and HER3 agents targeting highly aggressive drug resistant metastatic tumors, representing a major unmet need for patients."

On February 13, 2023 NovAccess Global Inc. ("NovAccess," the "company" or "we") reported that it has entered into an interest-free loan agreement with Jason M. Anderson, an independent member of our board of directors (Filing, 8-K, NovAccess Global, FEB 13, 2023, View Source [SID1234627204]). Reflecting his faith in NovAccess and our management team, Mr. Anderson loaned the company $8,500. The loan does not bear interest (except on default) and is due on the earlier of August 31, 2023 or our receipt of debt or equity financing of at least $3.0 million. We will use the proceeds of the loan for general working capital purposes.

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Also on February 9, we entered into a letter agreement (the "letter agreement") with AJB Capital Investments, LLC ("AJB"). In connection with a loan previously provided by AJB, we issued a promissory note to AJB on February 15, 2022 in the principal amount of $250,000 that was due February 16, 2023. The letter agreement extended the due date to May 9, 2023.

On May 5, 2022, we issued a promissory note to AJB in the principal amount of $1.0 million in connection with another loan from AJB. On February 9, 2023, AJB loaned us an additional $265,000, which was added to the May 2022 note. The $265,000 loan has an original issuance discount of 10% of the principal and bears interest at 10% a year. This loan is due on May 9, 2023. We will use the proceeds of the loan for general working capital purposes. Our chief executive officer Dwain K. Irvin guaranteed repayment of the $265,000 loan.

Also pursuant to the letter agreement, NovAccess paid AJB a commitment fee of 500,000 unregistered shares of the company’s common stock (the "commitment fee shares"). If AJB is unable to sell the commitment fee shares for $0.20 a share, then AJB may require NovAccess to issue additional shares or pay cash in the amount of the shortfall. We are also required to register the commitment fee shares for resale under the Securities Act.

Pursuant to the letter agreement, NovAccess also issued to AJB a common stock purchase warrant (the "warrant") to purchase 1.0 million shares of the company’s common stock for $0.20 a share. The warrant expires on February 9, 2028.

In connection with loans previously provided by AJB, we had issued two warrants to AJB to acquire up to 1.5 million shares of our stock for $1.50 a share. Pursuant to the letter agreement, the exercise price of these warrants was reduced to $0.20 a share.

The Anderson loan agreement and the AJB letter agreement and warrant are filed as exhibits to this Current Report on Form 8-K. The descriptions above are qualified in their entirety by reference to the full text of these documents.

Item 2.03 Creation of a Direct Financial Obligation or an Obligation under an Off-Balance Sheet Arrangement of a Registrant.

The disclosure included under Item 1.01 above is incorporated by reference to this Item 2.03.

Item 3.02 Unregistered Sales of Equity Securities.

The disclosure included under Item 1.01 above is incorporated by reference to this Item 3.02. The issuances of the commitment fee shares and warrant to AJB were exempt from registration under Section 4(a)(2) of the Securities Act of 1933.