On Jun. 6, 2022 Concert Pharmaceuticals, Inc. (NASDAQ: CNCE) reported the closing of its previously announced underwritten public offering of 10,000,000 shares of its common stock to the public at $4.75 per share (Press release, Concert Pharmaceuticals, JUN 6, 2022, View Source [SID1234615681]). The aggregate gross proceeds to Concert from this offering were $47.5 million, before deducting underwriting discounts and commissions and other offering expenses payable by Concert. Concert also announced the receipt of $18.9 million upon the exercise of tranche 1 warrants to purchase 3,981 shares of Series X1 Preferred Stock issued to BVF Partners L.P. and RA Capital Management in November 2021. Through the public offering and warrant exercise, Concert raised aggregate gross proceeds of $66.4 million.

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Jefferies and Truist Securities acted as joint book-running managers for the offering. JMP Securities, A Citizens Company, and Mizuho Securities acted as lead managers, and H.C. Wainwright & Co. acted as co-manager for the offering.

The offering was made only by means of a written prospectus supplement and prospectus forming part of a shelf registration statement previously filed with the Securities and Exchange Commission (SEC) and declared effective on November 16, 2020. The final prospectus supplement and accompanying prospectus relating to the offering was filed with the SEC and is available on the SEC’s website at www.sec.gov. Copies of the final prospectus supplement and accompanying prospectus may also be obtained by contacting Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, NY 10022, by telephone at (877) 821-7388, or by email at [email protected] or Truist Securities, Inc., Attention: Prospectus Department, 3333 Peachtree Road NE, 9th floor, Atlanta, Georgia 30326, by telephone at (800) 685-4786, email: [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 other 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 other jurisdiction.

On June 6, 2022 CStone Pharmaceuticals ("CStone", HKEX: 2616), a leading biopharmaceutical company focused on research, development, and commercialization of innovative immuno-oncology therapies and precision medicines, and Pfizer Inc. (NYSE: PFE) reported that the National Medical Products Administration (NMPA) of China has approved sugemalimab (Cejemly) for the treatment of patients with unresectable stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent or sequential platinum-based chemoradiotherapy (Press release, CStone Pharmaceauticals, JUN 6, 2022, View Source [SID1234615680]). Together with the previous approval of the treatment for first-line stage IV NSCLC patients, sugemalimab is now the only anti- PD-1/PD-L1 monoclonal antibody for both stage III and stage IV NSCLC patients.

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Dr. Frank Jiang, CEO of CStone, said, "We appreciate the NMPA for granting the new approval which is an important milestone in our journey to lead the treatment of lung cancer as China steps up efforts to support innovative therapies and address unmet needs. As a leading biopharma company in fostering precision medicines and immuno-oncology therapies, CStone has been spearheading multiple medical breakthroughs. With this approval, it will provide a new treatment option for stage III NSCLC patients, while demonstrating our prowess in advancing lung cancer treatments and bringing forward transformative drugs to the market. Partnerships are crucial to meet massive clinical needs of cancer patients. We will continue to work closely with Pfizer to deliver cutting-edge oncology therapies and improve the health of cancer patients in China."

Jean-Christophe Pointeau, China President of Pfizer Biopharmaceutical Group, says, "Committed to delivering ‘breakthroughs that change patients’ lives’, Pfizer has achieved a series of important breakthroughs in the field of immuno-oncology. After the approval of Stage IV NSCLC indication a few months ago, Cejemly achieved immediate commercialization across China, offering hopes to Chinese NSCLC patients with improved diagnosis and treatment solutions. We firmly believe that the approval of the new indication will allow more patients to benefit from this drug, bridge the gap and fulfill the unmet needs, especially the needs of unresectable Stage III NSCLC patients for immune consolidation therapy after sequential chemoradiotherapy. Cejemly is Pfizer’s strategic asset in immuno-oncology, and a paradigm for innovative strategic partnership with local biotech companies, like CStone guided by the slogan of "Science Will Win, Conquer Cancer Together". Starting from here, Pfizer will continue the exploration in this field, promote the upgrades and advances in immunodiagnostics and immunotherapy, offer more tailor-made, globally innovative solutions to Chinese cancer patients, and help to achieve the grand goal of "Healthy China 2030".

Professor Yi-Long Wu of Guangdong Provincial People’s Hospital, the Leading Principal Investigator on the GEMSTONE-301 study, said, "Patients with stage III NSCLC urgently need new treatment options, and the NMPA approval of sugemalimab brings them hope. The results from GEMSTONE-301 demonstrated that sugemalimab as a consolidation therapy had robust efficacy and a well-tolerated safety profile. It is now recommended by the Chinese Society of Clinical Oncology (CSCO) guidelines for this patient population. With proven clinical benefits, sugemalimab will potentially reshape the treatment landscape as a preferred immuno-oncology therapy for patients with mid- and late-stage lung cancer."

Dr. Jason Yang, Chief Medical Officer of CStone, said, "We are thrilled that sugemalimab has become the first anti- PD-1/PD-L1 monoclonal antibody approved for stage III NSCLC after concurrent or sequential chemoradiotherapy. The GEMSTONE-301 study has an innovative study design that enrolled patients with either concurrent or sequential chemoradiotherapy to better reflect real-world clinical practice and cover a broad patient population. We’ve also made significant progress in the registrational studies of sugemalimab in patients with esophageal squamous cell carcinoma, gastric cancer, and relapsed or refractory extranodal natural killer/T-cell lymphoma in a bid to benefit more cancer patients."

The NMPA approval is based on the GEMSTONE-301 study, a multicenter, randomized, double-blind phase 3 clinical trial, designed to evaluate the efficacy and safety of sugemalimab as a consolidation therapy in patients with unresectable stage III NSCLC without disease progression after concurrent or sequential chemoradiotherapy. Sugemalimab significantly improved patients’ progression-free survival (PFS). The risk of disease progression or death was reduced by 36%, together with encouraging overall survival (OS). Subgroup analyses demonstrated clinical benefits regardless of whether patients received prior concurrent or sequential chemoradiotherapy. Sugemalimab had a well-tolerated safety profile, and no new safety signals were observed. The results of the GEMSTONE-301 study were published in The Lancet Oncology in January 2022.

About Sugemalimab

The anti-PD-L1 monoclonal antibody sugemalimab was discovered by CStone using OmniRat transgenic animal platform, which allows creation of fully human antibodies in one step. Sugemalimab is a fully human, full-length anti-PD-L1 immunoglobulin G4 (IgG4) monoclonal antibody, which may allow a reduced risk of immunogenicity and toxicity for patients, a unique advantage over similar drugs.

Currently, the NMPA of China has approved sugemalimab (Cejemly) in combination with pemetrexed and carboplatin as first-line treatment of patients with metastatic non-squamous NSCLC, lacking epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) genomic tumor aberrations; and in combination with paclitaxel and carboplatin as first-line treatment of patients with metastatic squamous NSCLC; for the treatment of patients with unresectable stage III NSCLC whose disease has not progressed following concurrent or sequential platinum-based chemoradiotherapy.

With its proven therapeutic advantages, sugemalimab is set to be recommended by the 2022 CSCO clinical guidelines for the diagnosis and treatment of NSCLC, in combination with chemotherapy as the first-line treatment of patients with stage IV non-squamous/squamous NSCLC without driver alterations; or as a consolidation therapy in patients with stage III NSCLC after concurrent or sequential chemoradiotherapy.

CStone formed a strategic collaboration agreement with Pfizer that includes the development and commercialization of sugemalimab in mainland China, and a framework to bring additional Oncology medicines to the Greater China market.

On June 6, 2022 Enterome, a clinical stage biopharmaceutical company developing first-in-class immunomodulatory drugs based on its bacterial Mimicry drug discovery platform, reported that proof-of-concept immune response data and first clinical data from its Phase 1/2 clinical trial of EO2401 in combination with an immune checkpoint inhibitor (nivolumab, Opdivo) in patients with non-resectable adrenocortical carcinomas (ACC), treated with at least one line (but not more than two prior lines of systemic therapy), or without prior systemic therapy for advanced/metastatic disease (SPENCER trial, EOADR1-19, NCT04116658) (Press release, Enterome, JUN 6, 2022, View Source [SID1234615679]). The data1 were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, on June 4, 2022 in Chicago and virtually.

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EO2401 is Enterome’s first-in-class off-the-shelf OncoMimics cancer immunotherapy. It combines three OncoMimics peptides that closely mimic IL13Ra2, BIRC5 and FOXM1, all of which are known driver antigens present on aggressive solid tumors. In addition, EO2401 contains a CD4 helper peptide UCP2. Enterome selected these OncoMimics peptides using its Mimicry platform, which applies best-in-class biocomputational tools and bioassays to identify novel therapeutics from its proprietary database of 20+ million bioactive gut microbiome peptides and proteins.

Key highlights from the EO2401 poster presentation covering the Phase 1/2 SPENCER trial were:

Proof-of-concept immune response data

Immune monitoring of Cohort 2a demonstrates the ability of microbiome-derived peptides to induce a strong Tc1- skewed CD8+ T cell response with strong cross-reactivity against human selected tumor associated antigens.

The level of the specific CD8+ T cell immune responses against the microbiome-derived peptides comprising EO2401 were also found to correlate with clinical outcome (objective responses and progression-free survival).

Promising clinical outcome in sub-group of patients

The combination of EO2401 plus nivolumab was evaluated:

in patients with previously treated ACC (Cohort 2a, n=26) and
in patients who received no prior systemic therapy for advanced/metastatic disease (Cohort 2b, n=7)
Cohort 2a – group of patients showing benefit in objective tumor responses and time to progression

Analysis of Cohort 2a identified patients with clearly different efficacy outcomes, with one group showing benefit in objective tumor responses and time to progression, and another group with short progression-free survival (PFS) and short survival.

To refine the population for expansion in a randomized Phase 2 trial, different laboratory and clinical parameters were investigated as possible selection criteria.

No correlation was found between clinical outcome and tumor mutational burden, MSI-status, PD-L1 expression, serum cytokines/chemokines, or hormonal levels. However, the study found that patients in Cohort 2a who fulfilled the criteria of having received prior mitotane treatment, ECOG ≤ 1, ACC primary diagnosis > 9 months, max lesion size ≤ 125 mm, ≤ 3 organs involved, reduced lymphocytes ≤ grade 1 (n=14), demonstrated a clinical benefit vs patients not fulfilling these criteria (n=12), as follows:

Objective response rates (ORR) – 28.6% (95% CI 8.4; 58.1) vs 0% (95% CI 0.0; 26.5)
Disease control rates (DCR) – 64.3% (95% CI 35.1; 87.8) vs 8.3% (95% CI 0.2; 38.5)
Median progression-fee survival (PFS) – 3.9 months (95% CI 1.9; 9.2) vs 1.6 months (95% CI 0.5; 1.9)
Median survival – 13.0 months (95% CI 11.3; not evaluated) vs 2.1 months (95% CI 1.5; 7.4)
Cohort 2b – further follow up to be conducted

The clinical responses to EO2401 plus nivolumab observed in patients in Cohort 2b showed no benefit over the results from all patients in Cohort 2a, and further follow-up will be conducted.

Safety

The combination of EO2401, administered sub-cutaneously with the adjuvant Montanide ISA 51 VG, with nivolumab was well tolerated. The safety profile was consistent with the profile of nivolumab monotherapy, except the addition of local administration site reactions (occurring in 21% of patients).

Dr. Eric Baudin, Associate Professor and Head of the Endocrine Oncology Unit at the Institut Gustave Roussy (Villejuif, France) commented, "There has been no significant innovation in the treatment of advanced adrenal tumors and patients with this rare group of diseases are desperately in need of new effective therapies especially at relapse after first-line therapy. If confirmed, EO2401 in combination with nivolumab, represents the most promising therapy of the last three decades in this ultra rare cancer. I am pleased to be participating in this trial and to move forward into a randomized Phase 2 trial in this underserved patient population."

Dr. Jan Fagerberg, Chief Medical Officer of Enterome, said, "The data presented at ASCO (Free ASCO Whitepaper) for EO2401 in combination with nivolumab are very encouraging, with strong immune responses correlating to clinical outcome in patients having been previously treated for adrenocortical carcinoma. We are also pleased to have been able to define a set of clinical selection criteria that will enable us to refine a patient population for expansion in a Phase 2 randomized trial. We are on track to start this new trial in the coming months and look forward to the results in due course."

EO2401 in recurrent glioblastoma

At ASCO (Free ASCO Whitepaper), and separately announced today, Enterome presented the first clinical data from its Phase 1/2 clinical trials of EO2401 in combination with nivolumab +/- bevacizumab for the treatment of patients with recurrent glioblastoma (the ROSALIE trial, EOGMB1-18). View press release here.

About SPENCER

The SPENCER trial (EOADR1-19, NCT04187404) is a multicenter, open-label, Phase 1/2 study assessing the safety, tolerability, immunogenicity and preliminary efficacy of EO2401 in combination with the immune checkpoint inhibitor nivolumab in patients with adrenal tumors (adrenocortical carcinoma [ACC] and metastatic pheochromocytoma/paraganglioma [MPP]). The trial is expected to enrol at least 100 patients at clinical sites in Europe and the US.

References

Baudin, E. et al. EO2401, a novel microbiome-derived therapeutic vaccine for patients with adrenocortical carcinoma (ACC): Preliminary results of the SPENCER study. J Clin Oncol 40, 2022 (suppl 16; abstr 4596) doi: 10.1200/JCO.2022.40.16_suppl.4596

On June 6, 2022 Nouscom, a clinical stage immuno-oncology company developing off-the-shelf and personalized viral vectored immunotherapies, reported first data from the completed Phase 1 trial evaluating NOUS-209 in combination with anti-PD-1 checkpoint inhibitor (pembrolizumab) (Press release, NousCom, JUN 6, 2022, View Source [SID1234615678]). The data, presented yesterday in a poster discussion session at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, demonstrated NOUS-209 to be safe, highly immunogenic and with promising signs of clinical efficacy.

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NOUS-209, Nouscom’s lead product, is an off-the-shelf cancer vaccine targeting 209 shared neoantigens. It has been investigated in a Phase 1 clinical trial, administered in combination with the anti-PD-1 checkpoint inhibitor pembrolizumab, for the treatment of deficiency in Mismatch Repair/Microsatellite Instable High (dMMR/MSI-H) unresectable or metastatic gastric, colorectal and gastro-esophageal junction tumors.

The key findings from the study are as follows:

NOUS-209 continues to be safe and well tolerated
NOUS-209 immunogenicity was demonstrated by ex-vivo IFN-ɣ ELISpot assay in 83% of evaluable patients; vaccine induced immune responses were potent and broad
Early signs of clinical efficacy with 10 durable confirmed partial responses (PR), 4 durable stable disease (SD) and 6 progressive disease (PD)
Previously presented interim clinical and translational data of the combination indicated that neoantigen-specific CD8+ T cells expand and diversify only upon treatment with NOUS-209, and successfully infiltrate the tumor microenvironment to exert anti-tumor activity (presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper)1 in April 2022).

Professor Marwan G. Fakih, M.D., Medical Oncology Specialist at City of Hope’s Duarte California, and Study investigator said: "With clinical and translational data now available from all patients enrolled in this trial, it is encouraging to see NOUS-209 continuing to be safe, highly immunogenic and have signs of clinical efficacy. Durability of response in all PR and SD patients is particularly encouraging and provides hope for this patient group where there is still a significant unmet need. I look forward to seeing further clinical development of this compound in MSI-H patients."

Dr. Marina Udier, Chief Executive Officer of Nouscom, said: "These new data with all patients enrolled continues to reinforce our compelling and differentiating data for NOUS-209. This is a significant step for the company, validating the potency of our platform in inducing neoantigen specific CD8+ T cells, which are also able to successfully infiltrate tumors of metastatic cancer patients, exerting anti-tumor efficacy. We are actively working on the next stages of NOUS-209’s clinical development plan and look forward to announcing the start of the Phase 2 study in the second half of 2022."

Poster Presentation Details:

Title: First clinical and immunogenicity results including all subjects enrolled in a phase I study of NOUS-209, an off-the-shelf immunotherapy, with pembrolizumab, for the treatment of tumors with a deficiency in mismatch repair/microsatellite instability (dMMR)
The abstract is available here

References

AACR Presentation: Characterization of immune correlates of clinical activity for NOUS-209, an Off-the-Shelf immunotherapy, with Pembrolizumab for treatment of tumors characterized by Microsatellite Instability (MSI), Professor Marwan G. Fakih, M.D.
About NOUS-209

NOUS-209 is an off-the-shelf immunotherapy for Microsatellite Instable High (MSI-H) tumors. MSI-H tumors are characterized by a defective DNA mismatch repair system, which generates highly immunogenic frame shift peptides (frameshift mutations, FSPs) that are not found on healthy tissue.

NOUS-209 is designed to comprise 209 shared FSP neoantigens, selected by Nouscom’s proprietary GENESIS (GE(netic)NE(oantigen)S(election)I(n)S(ilico)) algorithm, on the basis that an average of 50 neoantigens on any patient’s tumor will be shared with those in NOUS-209. Nouscom’s heterologous prime/boost platform clones these FSPs into Great Ape Adenoviral (GAd) and Modified Vaccinia Ankara (MVA) vectors, to generate the viral-vectored vaccine, combined with other immunomodulators to harness the full power of the immune response by generating neoantigen specific CD8+ T cells, which successfully infiltrate tumor to exert anti-tumor activity.

NOUS-209 is in Phase 1 clinical trial (NCT04041310), a multicenter, open label, multiple cohorts, first-in-human clinical study of NOUS-209 in combination with pembrolizumab, designed to evaluate safety, tolerability and immunogenicity and to detect preliminary evidence of anti-tumor activity.

On June 6, 2022 The Ottawa Hospital, The Ontario Institute of Cancer Research ("OICR") and Intensity Therapeutics, Inc. ("Intensity"), a clinical-stage biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumoral cancer therapies designed to kill tumors and increase immune system recognition of cancers, reported that data from the INVINCIBLE study, a randomized, phase 2 presurgical Window-Of-Opportunity trial for Intratumoral INT230-6 comprising SHAO (dispersion enhancer), VINblastine (VIN) and Cisplatin (CIS) that is evaluating clinical and Biological Effects in patients with early-stage operable breast cancer (Press release, Intensity Therapeutics, JUN 6, 2022, View Source [SID1234615677]). The study, presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held in Chicago and virtually from June 3-7, 2022, reported data demonstrating efficacy and tolerability of INT230-6.

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Abstract Title: Intratumoral (IT) INT230-6 can cause tumor necrosis In Vivo: Preliminary results of a phase II randomized presurgical window-of-opportunity study in early breast cancers (the INVINCIBLE study).
First Author: Angel Arnaout, MD, FACS
Session Type/Title: Poster Session/Breast Cancer—Local/Regional/Adjuvant
Session Date and Time: Monday, June 6, 2022, 9:00 AM – 12:00 PM EDT
Location: In-Person & On Demand
Abstract Number: 605
Poster: 376

Copies of the presentation materials will also be available on the Intensity Therapeutics website on the publications and posters page, following completion of the live presentation.

"For a breast cancer patient, the typical waiting period of 2-6 weeks from diagnosis to surgery is a very anxious time. Surgeons and patients feel helpless, as there are currently no therapeutic options for the patient during this time," said Angel Arnaout, M.D., Scientist and Surgical Oncologist at the Ottawa Hospital, and Professor of Surgery at the University of Ottawa. "The active drug agents comprising INT230-6 remain in the tumor following injection and can cause tumor cell death and high levels of necrosis in multiple breast cancer subtypes including triple negative breast cancer, as demonstrated by Part 1 of this study. Interestingly, we also saw immune activation with a relative increase in the abundance of CD4 T naïve, B and NK cells, post treatment, and within the tumor microenvironment, a relative increase in abundance of CD8 memory T, CD4 naïve and B cells, post treatment, when comparing drug treated with control samples. The ability to use just one or two doses of this agent to elicit a rapid and marked cytotoxic and immune induction response within the tumor during the surgical waiting period, all without an increase in postoperative complications, is very novel and highly attractive to patients. We are excited about how this may shift the paradigm on how we treat cancer patients awaiting surgery, in general. We look forward to future studies to demonstrate how this intra-tumoral agent can have systemic benefit and long term impact in patients with breast cancer."

"INT230-6 is our novel, proprietary, locally-delivered, tumor dispersive anti-cancer product that has shown favorable clinical results as monotherapy in a basket study of patients with advanced, relapsed and refractory disease," said Lewis H. Bender, President and Chief Executive Officer of Intensity Therapeutics. "These first results reported from the INVINCIBLE breast cancer study provide evidence and support for the potential of our drug in treating local disease prior to surgery. The data from Part I of the INVINCIBLE study show that INT230-6 is well tolerated and, as we see in metastatic disease, elicits both rapid direct tumor killing and immune activating effects. We anticipate completing enrollment of Part II this summer and reporting the full patient study results at a future oncology conference."

About the INVINCIBLE Study
The INVINCIBLE study is a phase II, randomized, open label, multi-center study, expected to enroll up to 90 women with newly diagnosed operable early-stage intermediate or high-grade T1-T2 invasive breast cancers who are randomly allocated (2:1) prior to resection to IT injections of INT230-6, no treatment or saline sham injection. The study has two parts. Part I (N=29), now complete, randomized patients 2:1 to either 1-3 doses of INT230-6 injected weekly or no treatment, 2 to 5 weeks prior to surgery (lumpectomy or mastectomy). The purpose of this portion of the trial was to evaluate safety, feasibility, and optimal drug dosing. Part II is a double-blind, randomized arm of up to 60 patients, where patients will be randomized 2:1 to receive one or two IT doses of INT230-6 vs. saline injection. The objective of using saline will be to rule out the potential confounding effect of hydrostatic pressure on tumor necrosis. The results of Part II will further evaluate the potential cytotoxic, immunomodulatory and other biologic effects of INT230-6 and its role as a potential cancer therapy in breast cancer patients awaiting surgery. The INVINCIBLE Study is being conducted under a Health Canada (HC) approved Clinical Trial Application (CTA), under the direction and supervision of Principal Investigator, Dr. Angel Arnaout. OHRI will conduct subject enrollment and treatment, and evaluate clinical responses. OICR will analyze subject immune responses and conduct biomarker analyses.

About Potential INT230-6 Approval Pathways in the Presurgical Setting
The U.S Food and Drug Administration (FDA) instituted its Accelerated Approval Program to allow for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint. Pathological complete response (pCR) is an accepted FDA accelerated approval criterion for approval in high risk breast cancer, such as TNBC subtype. pCR is defined as the absence of residual invasive and in situ cancer after evaluation of the complete resected breast specimen and lymph nodes following completion of neoadjuvant systemic therapy.

Data from the INVINCIBLE study will provide an understanding of the effect of INT230-6 on cancer cell proliferation and tumor necrosis. If INT230-6 causes increased tumor necrosis with good safety, then the addition of INT230-6 to the existing or a modified neoadjuvant (presurgical) systemic standard-of-care treatment regimen may increase pCR rates in TNBC. In November of 2020, Intensity Therapeutics met with FDA and discussed the potential use of INT230-6 in the presurgical neoadjuvant breast cancer setting in an accelerated approval program.

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 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 and the induction of an anti-cancer systemic immune response resulting in shrinkage of uninjected tumors.