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Iovance Biotherapeutics Provides Update on Biologics License Application Submission for Lifileucel in Advanced Melanoma

On November 18, 2022 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA) reported that its ongoing rolling Biologics License Application (BLA) submission to the U.S. Food and Drug Administration (FDA) for lifileucel is expected to be completed in the first quarter of 2023 (Press release, Iovance Biotherapeutics, NOV 18, 2022, View Source [SID1234624239]).

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As part of an amendment to the ongoing investigational new drug application (IND) submitted during the third quarter of 2022, Iovance received recent FDA feedback regarding supplemental assay validation information and comparability data for lifileucel. Iovance will address these FDA comments promptly and will now complete its rolling BLA submission during the first quarter of 2023.

Lifileucel is an investigational tumor infiltrating lymphocyte (TIL) therapy for patients with advanced (unresectable or metastatic) melanoma who progressed on or after prior anti-PD-1/L1 therapy, and targeted BRAF/MEK inhibitor therapy where appropriate. There are no FDA approved therapies in this treatment setting.

Frederick Vogt, Ph.D., J.D., Iovance’s Interim President and Chief Executive Officer stated, "We continue to make substantial progress with our ongoing BLA submission and remain close to the finish line. The FDA has provided recent valuable feedback to the IND application and remains supportive during the rolling BLA submission process. Iovance is fully committed to securing FDA approval as soon as possible to deliver the first individualized, one-time cell therapy for advanced melanoma patients, who have a significant unmet medical need."

As previously announced, Iovance held a successful pre-BLA meeting in July 2022, and the rolling BLA commenced in August 2022. A rolling BLA allows Iovance to submit portions of the BLA to the FDA on an ongoing basis, which enables the FDA to begin review as early as possible as documents are received. The rolling BLA submission and eligibility for priority review are benefits available under the FDA’s guidance on expedited programs for serious conditions. The FDA previously granted a regenerative medicine advanced therapy (RMAT) designation for lifileucel in advanced melanoma.

The BLA submission for lifileucel is supported by positive clinical data from the C-144-01 clinical trial in patients with advanced melanoma. The Phase 3 trial of lifileucel in combination with pembrolizumab in frontline advanced melanoma, on track to begin in late 2022, is intended to serve as a confirmatory study and is expected to be well underway at the time of a potential approval.

Investor Webcast on Friday, November 18, 8:00 a.m. ET

Iovance will host a webcast on Friday, November 18 at 8:00 a.m. ET to discuss this corporate update. To participate in the webcast, please register at https://register.vevent.com/register/BI99a18daf00f04087b70d9c6b45008d6f. The live webcast and replay can be accessed in the Investors section of the company’s website at IR.Iovance.com.

Entry Into a Material Definitive Agreement

On November 18, 2022, Iovance Biotherapeutics reported that entered into a new Open Market Sale Agreement (the "Sales Agreement") with Jefferies LLC ("Jefferies") with respect to an at the market offering program, under which the Company may, from time to time in its sole discretion, issue and sell through Jefferies, acting as sales agent, up to $500.0 million of shares of the Company’s common stock, par value $0.000041666 per share (the "Common Shares") (Filing, 8-K, Iovance Biotherapeutics, NOV 18, 2022, View Source [SID1234624238]). The Prior Sales Agreement (as defined below) was terminated, and the Sales Agreement replaces the Prior Sales Agreement.

The issuance and sale, if any, of the Common Shares by the Company under the Sales Agreement will be made pursuant to a prospectus supplement, dated November 18, 2022, to the Company’s registration statement on Form S-3ASR, originally filed with the Securities and Exchange Commission on May 27, 2020, which became effective immediately upon filing.

Pursuant to the Sales Agreement, Jefferies may sell the Common Shares by any method permitted by law deemed to be an "at the market" offering as defined in Rule 415 of the Securities Act of 1933, as amended (the "Securities Act"). Jefferies will use commercially reasonable efforts consistent with its normal trading and sales practices to sell the Common Shares from time to time, based upon instructions from the Company (including any price or size limits or other customary parameters or conditions the Company may impose).

The Company will pay Jefferies a commission of up to 3.0% of the gross sales proceeds of any Common Shares sold through Jefferies under the Sales Agreement.

The Company is not obligated to make any sales of Common Shares under the Sales Agreement. The offering of Common Shares pursuant to the Sales Agreement will terminate upon the earlier to occur of (i) the issuance and sale, through Jefferies, of all Common Shares subject to the Sales Agreement and (ii) termination of the Sales Agreement in accordance with its terms.

The Sales Agreement contains representations, warranties and covenants that are customary for transactions of this type. In addition, the Company has agreed to indemnify Jefferies against certain liabilities, including liabilities under the Securities Act and the Securities Exchange Act of 1934, as amended.

The foregoing description of the Sales Agreement is not complete and is qualified in its entirety by reference to the full text of the Sales Agreement, a copy of which is filed herewith as Exhibit 1.1 to this Current Report on Form 8-K and is incorporated herein by reference.

The legal opinion of DLA Piper LLP (US) as to the legality of the Common Shares is being filed as Exhibit 5.1 to this Current Report on Form 8-K.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy the securities discussed herein, nor shall there be any offer, solicitation or sale of the securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction.

Intensity Therapeutics Reports Use of INT230-6 Alone or in Combination with Ipilimumab Shows Evidence of Direct Tumor Necrosis and Promising Overall Survival Results in Adult Subjects with Metastatic Sarcomas at the Connective Tissue Oncology Society (CTOS) 2022

On November 18, 2022 Intensity Therapeutics, Inc. ("Intensity"), a clinical-stage biotechnology company focused on the discovery and development of proprietary immune-based intratumoral cancer therapies designed to kill tumors and increase immune system recognition of cancers, reported that data from its open-label phase 1/2 study of novel lead asset, INT230-6, as a monotherapy or in combination with ipilimumab in adult subjects with metastatic sarcomas, will be presented in an oral podium presentation, at the Connective Tissue Oncology Society Annual Meeting (CTOS) being held at the Vancouver Convention Center in Vancouver, BC, Canada from November 16 -19, 2022 (Press release, Intensity Therapeutics, NOV 18, 2022, View Source [SID1234624236]).

"Preliminary data suggests that INT230-6, as a monotherapy or in combination with the immune checkpoint blocker ipilimumab, demonstrates direct tumor killing in soft tissue sarcoma (STS) and elicits an anti-cancer immune response within the injected tumor," stated Matthew Ingham, M.D., assistant professor of medicine in the Division of Hematology and Oncology, Columbia University Vagelos College of Physicians and Surgeons, and a principal investigator for the trial. "To date, INT230-6 treatment related adverse events are mostly low grade and the drug is well-tolerated either as a monotherapy or in combination with ipilimumab. Additionally, in patients who had 40% or more of their tumor burden treated with INT230-6, an exploratory analysis showed that overall survival was improved when compared to historical benchmarks for this patient population."

Lewis H. Bender, President and Chief Executive Officer of Intensity Therapeutics, added, "The compelling safety and efficacy results from use of our drug in treating such a deadly and hard-to-treat cancer as soft tissue sarcomas underscore the potential of this treatment. The promising data supports our belief that INT230-6 could show clinical benefit with lower levels of off-target side effects compared to standard chemotherapies. We have designed a randomized phase 3 trial protocol to evaluate INT230-6 versus standard of care in patients with advanced soft tissue sarcomas and look forward to initiation of the study."

Abstract ID: 1301741
Title: Intratumoral INT230-6 (Cisplatin, Vinblastine, Shao) Alone or with Ipilimumab Prolonged Survival with Favorable Safety in Adults with Refractory Sarcomas (NCT03058289)
Session: Session 9: Immunology & Immunotherapy
Session Date Friday, November 18, 2022
Time: 3:30 PM – 5:00 PM PST
First Author: Matthew Ingham, M.D.
Presenter: Christian Meyer, M.D.
The presentation will be accessible on the "Publications, Papers and Posters" section of Intensity’s website at: View Source

The data presented included results from 29 patients with different metastatic sarcomas treated with INT230-6 either as a monotherapy (n=15), or in combination with ipilimumab (n=14). The enrolled patients’ cancer progressed following a median of three prior lines of therapy (range 0 to 9) including all approved, appropriate therapies for a subject’s particular cancer. Demographics were similar in subjects enrolled in monotherapy and checkpoint inhibitor combination arms. Pharmacokinetic data shows that >95% of the active agents remain in the tumor. Immunohistochemistry shows that there is an increase in the immune cell infiltration pre and post dose.

Study IT-01 is a single arm study; however, published clinical phase 1/2 basket trials in sarcoma report mOS, ranging from 230 to 290 days (Jones et. al., Cassier et. al., Subbiah et. al.). Using the Subbiah study data a synthetic control group Kaplan Meier (KM) survival curve was generated. The overall survival of the control, all INT230-6 patients and those receiving a cumulative dose of greater than 40% of their total tumor burden (TTB), are shown in the below table. Subjects receiving combination with ipilimumab have not yet reached median survival with 345 days median follow-up. There have been only 2 deaths reported in the combination group as of data cut-off. Sarcoma subtypes may differ between groups and data is still early.

Sarcoma phase 1/2 studies Control (Subbiah) INT230-6 all INT230-6 >40% TTB INT230-6 + IPI
Median OS 205 days 649 days 715 days Not yet reached*
Confidence Interval – (195, 1352) (649, 1352)
Sample size 56 15 11 14
About INT230-6

INT230-6, Intensity’s lead proprietary investigational product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity’s proprietary DfuseRx℠ technology platform. The drug is composed of two proven, potent anti-cancer agents, cisplatin and vinblastine, and a penetration enhancer molecule (SHAO) that helps disperse potent cytotoxic drugs throughout tumors for diffusion into cancer cells. These agents remain in the tumor resulting in a favorable safety profile. In addition to local disease control, direct killing of the tumor by INT230-6 releases a bolus of neoantigens specific to the patient’s malignancy, leading to engagement of the immune system and systemic anti-tumor effects. Importantly, these effects are mediated without the immunosuppression of concomitant systemic chemotherapy.

INT230-6 is currently being evaluated in several phase 2 cohorts (NCT03058289) in patients with various advanced solid tumors as part of Study IT-01. In 2019, the Company signed a clinical collaboration agreement with Merck Sharpe & Dohme (Merck) to evaluate the combination of INT230-6 and KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 (programmed death receptor-1) therapy, in patients with advanced pancreatic, colon, squamous cell and bile duct malignancies. In 2020, the Company executed a clinical collaboration agreement with Bristol-Myers Squibb Company to evaluate the combination of INT230-6 with Bristol-Myers Squibb’s anti-CTLA-4 antibody, ipilimumab, in patients with advanced liver, breast and sarcoma cancers. In 2021, the Company executed agreements with the Ottawa Hospital Research Institute and the Ontario Institute of Cancer Research to study INT230-6 in a randomized controlled neoadjuvant phase 2 study in women with early stage breast cancer (the INVINCIBLE study) (NCT04781725).

HiFiBiO Therapeutics Announces Clinical Trial Supply Agreement to Evaluate HFB200603 in Combination with Tislelizumab in Patients with DIS™ Selected Advanced Solid Tumors

On November 18, 2022 HiFiBiO Therapeutics, a multinational clinical-stage biotherapeutics company, reported a second clinical trial supply agreement with Novartis to evaluate HiFiBiO’s HFB200603, a novel anti-BLTA monoclonal antibody in combination with tislelizumab, Novartis anti-PD-1 immune checkpoint inhibitor, for the treatment of advanced solid tumor indications preselected by HiFiBiO’s proprietary Drug Intelligence Science (DIS) platform (Press release, HiFiBiO Therapeutics, NOV 18, 2022, View Source [SID1234624235]).

"The continuation of our collaboration with Novartis bring us a step closer to realize our vision to provide potentially curative immunotherapies for each and every patient using our Drug Intelligence Science (DISTM) approach for novel drug discovery and development" said Liang Schweizer, Ph.D., Founder, Chairperson and CEO at HiFiBiO Therapeutics.

Under the terms of the agreement, HiFiBiO Therapeutics will maintain control of the HFB200603 program, including global R&D and commercial rights. Novartis has agreed to supply tislelizumab for use in combination with HFB200603.

HFB200603

HFB200603 was identified using HiFiBiO single cell platform as a single-digit nanomolar binder to human and cynomolgus BTLA, capable of blocking BTLA interaction with its ligand HVEM, reversing HVEM-mediated immune suppressive effects, and inducing the production of inflammatory cytokines in the tumor microenvironment of different human tumor types. HFB200603 synergizes with anti-PD-1 to enhance IFN-γ production and demonstrates favorable developability, pharmacokinetic and safety profiles.

Tislelizumab
Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages. In pre-clinical studies, binding to Fcγ receptors on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells.

Candel Therapeutics Announces Oral Presentation of Updated Data from its Phase 1 Clinical Trial of CAN-3110 in 41 Patients with Recurrent High-Grade Glioma at the Society for Neuro-Oncology 27th Annual Meeting

On November 18, 2022 Candel Therapeutics, Inc. ("Candel" or "the Company") (Nasdaq: CADL), a clinical stage biopharmaceutical company developing novel viral immunotherapies, reported presentation of updated data from a phase 1 clinical trial of CAN-3110 in patients with recurrent high-grade glioma (rHGG) (Press release, Candel Therapeutics, NOV 18, 2022, View Source [SID1234624233]). An overview of this data will be presented in-person at the Society for Neuro-Oncology (SNO) 27th Annual Meeting (SNO) today starting at 5:30 pm ET in Tampa, Florida.

Data will be reported from 41 patients who were administered CAN-3110, with 40 patients having received a single injection and one patient having received two injections. There were no dose-limiting toxicities. The median overall survival was 11.6 months. In-depth biomarker analyses show a statistically significant expansion of activated CD4+ and CD8+ T cells effector cells in multiple tumor lesions following a single injection of CAN-3110. Diversity of the T cell receptor repertoire after CAN-3110 administration was reported to be associated with overall survival. Next, the Company will examine whether multiple injections of CAN-3110 over time could lead to further improvement in overall survival (NCT03152318, clinicaltrials.gov).

"Patients with high-grade glioma whose cancer has recurred following initial standard of care treatments face a daunting challenge, with most succumbing to their disease within months due to a lack of effective therapies," said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel Therapeutics. "We believe CAN-3110 is the first HSV-based viral

immunotherapy candidate designed to leverage the ICP34.5 gene, which plays a key role in the viral anti-host response. The absence of observed dose-limiting toxicities in 41 patients and a median overall survival rate of one year provides clinical validation for this unique construct. This trial has clearly shown that a single injection of CAN-3110 can convert the highly immunosuppressive tumor microenvironment in recurrent high-grade glioma into a ‘hot’ tumor. We are now determining if multiple injections of CAN-3110 can fundamentally transform this universally fatal brain cancer."

CAN-3110 is unique in that it is designed to express a copy of the viral ICP34.5 gene, which is critical for viral replication and anti-host responses, under the transcriptional control of the tumor specific Nestin promoter. This approach is intended to restrict viral replication and virulence to the tumor cells, protecting healthy tissues while maintaining its anti-tumor responses.

Details on the presentation at SNO are as follows:

Oral Presentation Title: Enriched TCR/BCR VDJ rearrangements correlate with MRI and survival outcomes in patients with recurrent high-grade glioma treated with CAN-3110

About CAN-3110

CAN-3110 is a herpes simplex virus (HSV) replication-competent viral immunotherapy candidate engineered to enhance selective killing of malignant cells while sparing healthy normal neighboring cells. CAN-3110 has been shown to selectively express ICP34.5, a key gene in HSV replication, in tumor cells that overexpress Nestin, a cytoskeletal protein. Nestin is highly expressed in glioma cells and other tumor tissue, but is absent in the healthy adult brain. The effects of multiple doses of CAN-3110 in recurrent glioblastoma are currently being evaluated in an ongoing phase 1 clinical trial.