On November 10, 2022 Anaveon, a clinical stage, immuno-oncology company, reported updated clinical data from the ongoing Phase I study of ANV419 in patients with solid tumors at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting, being held from November 8–12, 2022, at the Boston Convention and Exhibition Center in Boston, MA (Press release, Anaveon, NOV 10, 2022, View Source [SID1234623687]).

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In the ongoing study, 29 patients in 10 dosing cohorts with different cancers progressing after standard therapy, received ANV419 monotherapy once every 14 days at doses up to 364 µg/kg in two-week cycles as an intravenous infusion over 15 minutes. ANV419 is a powerful and selective IL-2 agonist, which has been specifically designed to enable the delivery of high dose IL-2 to patients, with a favourable safety and tolerability profile.

In the study, ANV419 was generally well tolerated, and all drug related events were manageable, reversible, and responsive to supportive care therapy. The most common drug related AEs were low grade (G1 or G2) fever, chills, vomiting and fatigue. No patients have withdrawn from the study due to AEs and no dose limiting toxicities were observed up to and including 243 µg/kg.

In this heavily pre-treated population, 5 patients continue to receive treatment. At ANV419 doses ≥108 µg/kg, 66% of patients achieved at least disease stabilization (9 SD, 1 PR). One patient who continues ANV419 treatment, has a confirmed Partial Response (as per RECISTv1.1) with 31% tumor shrinkage after 2 weeks of ANV419 and a sustained and deepening response of 56% shrinkage at 6 cycles (12 weeks) of ANV419.

Pharmacodynamic evaluation of ANV419 on day 4 post-dosing (cycle 1 and 2) showed a selective and dose dependent proliferation of CD8+ T and NK cells, with a lower increase of proliferating Tregs. ANV419 half-life increases up to 28 hours with increasing doses and ANV419 concentration is overall stable between cycles.

Anaveon has initiated Ph I/II studies to demonstrate efficacy of ANV419 in metastatic melanoma and multiple myeloma.

Dr. Elena Garralda at the Hospital Universitari Vall d’Hebron in Barcelona, and lead investigator on the study said, "These early clinical data are encouraging and I believe ANV419 has the potential to become an important component of therapy for patients with cancer."

Preclinical data for ANV419 in combination with checkpoint inhibitors that builds on the data presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022 in September were also presented at SITC (Free SITC Whitepaper). These continue to demonstrate broad activity of ANV419 on effector cells, supporting the initiation of Phase II studies assessing ANV419 treatment in indications in which CD8 T cells and NK cells are involved in tumor resolution as well as supporting combination studies with checkpoint inhibitors and treatments acting through antibody-dependent cellular cytotoxicity.

"It is very exciting to see the continued safety and tolerability of ANV419 at higher doses, demonstrating the ability of ANV419 to deliver high molar equivalents of IL-2 in a tolerable and convenient way. Importantly, tumor response continues to deepen," added Christoph Bucher, MD, Chief Medical Officer of Anaveon. "We have initiated our first Phase II trial, investigating the efficacy of ANV419 in patients with cutaneous melanoma and we look forward to starting our Phase II study in Multiple Myeloma, whilst also broadening our pipeline with therapies that we expect will be effective as both standalone and combination therapies."

Abstracts are available on the SITC (Free SITC Whitepaper) website and the accompanying posters will be available in the publications section of Anaveon’s website.

Details of the poster presentations are:

Title: Phase I dose escalation study in patients with advanced solid tumors with ANV419, a novel fusion protein selective for IL-2Rβ/γ
Authors: Christoph Bucher, MD; Guzman Alonso, Dr; Juanita Lopez; Emiliano Calvo; Markus Joerger, MD; Vicky Sanchez Perez, MD; Elena Corral, MD; Daniela Di Blasi, PhD; Kirsten Richter, PhD; Christoph Huber, PhD; Julie Mouton; Silvio Costanzo; Sangeeta Jethwa, MD; Elena Garralda, MD; Heinz Läubli, MD PhD
Presenter: Daniela Di Blasi, PhD
Abstract Number: 631
Date & Time: Thursday, November 10, 2022 from 9 a.m. to 9 p.m. EST

Title: ANV419 is a novel CD122-biased IL-2/anti-IL-2 fusion protein showing increased efficacy in combination with checkpoint inhibitors and treatments acting through antibody dependent cellular cytotoxicity
Authors: Christoph Huber, PhD; Kirsten Richter, PhD; Laetitia Petersen; Nicole Egli; Patrizia Murer, PhD
Presenter: Christoph Huber, PhD
Abstract Number: 1099
Date & Time: Thursday, November 10, 2022 from 9 a.m. to 9 p.m. EST

Anaveon is undertaking a Phase I/II study to evaluate the safety, dosing and clinical activity of its lead program, ANV419, a powerful and selective interleukin-2 (IL-2) agonist in patients with solid tumors. The Company is pursuing multiple parallel Phase II programs in order to explore the full therapeutic potential of ANV419. In addition, Anaveon continues its work in developing follow-on compounds to expand on the success of ANV419 by delivering the IL-2 agonist to tumor fighting cells and thus expand the therapeutic potential into less immunogenic tumors. Alongside this, the Company is building on its cytokine engineering expertise with preclinical-stage programs harnessing the power of cytokines for therapeutic purposes.

On November 10, 2022 Bicycle Therapeutics plc (NASDAQ:BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported that preclinical data for BT7480, a novel Bicycle tumor-targeted immune cell agonist (Bicycle TICA), and BT7455, an EphA2/CD137 Bicycle TICA, will be presented in five poster presentations at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37th Annual Meeting, being held in Boston, M.A. and virtually on November 8-12, 2022 (Press release, Bicycle Therapeutics, NOV 10, 2022, View Source [SID1234623686]).

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On November 10, 2022 Pulmatrix (NASDAQ: PULM), a clinical-stage biopharmaceutical company developing innovative inhaled therapies to address serious disease using its patented iSPERSE technology, reported third quarter financial results for 2022 and provided a corporate update related to its development programs (Press release, Pulmatrix, NOV 10, 2022, View Source [SID1234623685]).

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Ted Raad, Chief Executive Officer of Pulmatrix commented, "In this quarter we have advanced both PUR3100 and PUR1900 towards important data catalysts. We completed patient dosing for PUR3100, our orally inhaled dihydroergotamine (DHE) being developed for the treatment of acute migraine, in a Phase 1 study with data expected to be released in early Q1 2023. In addition to safety and tolerability, the study will evaluate the pharmacokinetics of PUR3100 compared to intravenous DHE. This will allow us to better understand the potential efficacy and tolerability profile of PUR3100, which we believe could be beneficial to patients suffering from acute migraine. We also commenced study start-up activities for the PUR1900 Phase 2 study and remain on track to initiate patient dosing in the first quarter of 2023. PUR1900 has the potential to be the first approved therapy for the treatment of Allergic Bronchopulmonary Aspergillosis (ABPA) in patients with asthma."

Third Quarter 2022 and Recent Program Highlights

PUR1900 in development for ABPA

Pulmatrix initiated study start-up activities for the Phase 2 safety and efficacy study of PUR1900 in patients with asthma and ABPA. This will include a 16-week dosing regimen and endpoints that would potentially support a Phase 3 trial.
PUR3100 in development for acute migraine

On September 26, 2022, Pulmatrix announced completion of patient dosing in its Phase 1 trial evaluating PUR3100.
Phase 1 study database lock to occur in November with top-line data anticipated to be released in early Q1 2023.
PUR1800 in development for Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD)

Pulmatrix is analyzing data from the completed Phase 1b clinical study of PUR1800 for AECOPD for presentation at a relevant medical conference in 2023. These data will inform the design of a potential Phase 2 study in the treatment of AECOPD.
Third Quarter 2022 Financial Results

Revenues increased $0.8 million to $1.9 million for the three months ended September 30, 2022 compared to $1.1 million for the same period in 2021. The increase in revenue was due to $1.9 million in revenue in the three months ended September 30, 2022 for the PUR1900 program related to the Cipla Agreement compared to no revenues for the three months ended September 30, 2021. This was partially offset by no revenues in the three months ended September 30, 2022 for the PUR1800 program compared to $1.1 million for the three months ended September 30, 2021.

For the three months ended September 30, 2022, research and development expenses increased $1.3 million to $5.3 million compared to $4.0 million for the same period in 2021. The increase was primarily due to increased spending of $1.5 million in clinical costs related to the PUR1900 program, $0.6 million in employment costs and $0.2 million in facility costs. This amount was partially offset by a $1.0 million decrease in non-clinical and clinical costs related to the PUR1800 program.

General and administrative expenses were unchanged at $1.7 million for the three months ended September 30, 2022 compared to the same period in 2021.

During the three months ended September 30, 2022, the Company sold 252,013 shares of its common stock at a weighted-average price of approximately $5.70 per share, for net proceeds of approximately $1.4 million, under the At-The-Market Sales Agreement established with H.C. Wainwright & Co., LLC in May 2021.

Cash and cash equivalents as of September 30, 2022 was $40.7 million. As of November 10, 2022, Pulmatrix expects its existing cash and cash equivalents will enable it to fund operating expenses and capital expenditure into the second quarter of 2024.

On November 10, 2022 Cellectis (the "Company") (Euronext Growth: ALCLS – NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported that preclinical data will be presented on TALEN-edited smart CAR T-cells overcoming key challenges of targeting solid tumors at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37th Annual Meeting (Press release, Cellectis, NOV 10, 2022, View Source [SID1234623684]).

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The data will be presented today in two poster sessions titled: "Multi-armored allogeneic MUC-1 CAR T-cells efficiently control triple negative breast cancer tumor growth" (Poster Number: 217) and "TALEN-edited smart CAR T-cells leverage solid tumor microenvironment for specific and effective immunotherapy" (Poster Number: 325).

The poster presentations highlight the following preclinical data:

Multi-armored allogeneic MUC-1 CAR T-cells efficiently control triple negative breast cancer tumor growth

· This poster highlights TALEN-edited smart CAR T-cells targeting MUC1- expressing solid tumors.

· MUC1 is a tumor-associated antigen that is overexpressed in triple-negative breast cancer (TNBC) and other solid tumor malignancies.

· MUC-1 CAR T-cells infiltrate tumors more efficiently and extend survival when enhanced with attributes catered towards the tumor microenvironment (TME) of TNBC tumors.

· TGFBR2 knock-out (KO) circumvents the inhibitory effects of TGFβ1, and IL-12 release follows CAR T-cell activation pattern restricting it to the tumor site for increased safety.

· Enhanced MUC-1 CAR T-cells could address some of the current challenges in development of CAR Ts for TNBC patients with unmet medical needs.

· Overall, we can efficiently generate allogeneic CAR T-cells and engineer them to overcome several key challenges of immune suppressive solid tumors.

TALEN-edited smart CAR T-cells leverage solid tumor microenvironment for specific and effective immunotherapy

· This poster highlights innovative T-cell engineering strategies designed to increase the activity of CAR T-cells for solid tumors while mitigating toxicity risk.

· Therapeutic efficacy of CAR T-cell therapy has so far been restricted to only a few malignancies, with solid tumors proving to be especially recalcitrant to efficient therapy. Our TALEN-based gene editing platform allows innovative T cell engineering strategies that can combat some of the challenges posed by CAR T cell development for solid tumors.

· Inducible expression of a tumor-antigen directed CAR by a constitutive CAR specific to TME cues greatly enhanced anti-tumor activity, while limiting ‘on target, off-tumor’ cytotoxicity. Additionally, CAR-induced gene expression could boost anti-tumor CART only within the TME.

· Cellectis’ gene editing strategies could increase CAR T cell persistence and anti-tumor activity while staying restricted to the tumor milieu.

· This proof-of-concept study demonstrates the feasibility of developing CART cell engineering strategies that can improve solid tumor targeting while mitigating potential safety risks, paving the way for clinical development.

Laurent Poirot, Ph.D., Senior Vice President Immunology at Cellectis, noted:

"Using our TALEN-based gene editing platform, we have presented innovative T cell engineering strategies that can combat some of the challenges posed by CAR T cell development for solid tumors. We are mitigating potential safety risks, paving the way for clinical development for patients with unmet medical needs."

Presentations will occur today, from 9:00AM until 9:00PM ET, Hall C.

A copy of both poster presentations will be available on Cellectis’ website here, shortly after the event.

On November 10, 2022 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company focused on developing first-in-class therapeutics that combine both targeted and immune-mediated mechanisms, reported the presentation of data on TPST-1120, an oral selective peroxisome-proliferator activated receptor-alpha (PPAR-α) antagonist, and TPST-1495, a dual antagonist of both EP2 and EP4 prostaglandin (PGE2) receptors, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting taking place November 10-12, 2022 in Boston, MA (Press release, Tempest Therapeutics, NOV 10, 2022, View Source [SID1234623683]).

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The biomarker results presented from the TPST-1120 Phase 1 clinical study demonstrate pharmacodynamic changes in circulating blood in patients who received clinical benefit from therapy that are consistent with blocking the activity of PPAR-α. In addition, data presented from TPST-1495 showed that its dual antagonism of EP2 and EP4 generated significantly greater immune activation in human immune cells and anticancer activity in mouse tumor models than single inhibitors of either receptor, or the COX-2 inhibitor, celecoxib.

"As we advance the Tempest pipeline, we continue to generate results that validate and differentiate the novel approaches of our product candidates," said Tom Dubensky, Ph.D., president of Tempest. "For patients who responded to treatment with TPST-1120 in our Phase 1 study, we have identified potential biomarkers in the peripheral blood of immune activation and alleviation of immune suppression. These discoveries may enable us to identify patient populations in future clinical studies that are most likely to benefit from treatment with TPST-1120."

TPST-1120: "Pharmacodynamic and Predictive Biomarkers Associated with Response in Cancer Patients Treated with TPST-1120: a First-in-class, Small Molecule Antagonist of Peroxisome-Proliferator Activated Receptor-Alpha"

In a late-breaking poster presentation, data from a Phase 1 trial with monotherapy and nivolumab combination arms were used to assess gene expression changes in post-treatment whole blood from 30 patients and to perform baseline mutational analysis on ctDNA to identify potential biomarkers. The data showed that seven genes were modulated by TPST-1120 exposure (p<0.05), including genes associated with enhanced immune responsiveness (CXCL16, TNFRSF1A), stimulation of monocytes or macrophages (ITGAX, FCGR2A) and PPAR-α blockade (NCF4). The results were consistent across monotherapy and combination arms. Patients in the combination arm who had a partial response (PR) to treatment had significant elevations (p<0.05) in multiple genes, including those associated with Th17 development (RORC), lipid transport (APOE) and down-regulation of CD155, a TIGIT ligand. Mutational analysis revealed that patients with a PR or stable disease were more likely to bear mutations in isocitrate dehydrogenase (IDH) and phosphatase and tensin homolog (PTEN) compared to patients with progressive disease.

TPST-1495: "Dual Blockade of the EP2 and EP4 PGE2 Receptors with TPST-1495 is an Optimal Approach for Drugging the Prostaglandin Pathway"

In a second presentation, the data demonstrated that TPST-1495 was more effective than EP2 and EP4 single antagonists, and the COX-2 antagonist, celecoxib, in mouse and human whole blood assays. TPST-1495 conferred a near complete restoration of immune function in cellular assays, even in the presence of high PGE2 concentrations. In lung carcinoma tumors and in a spontaneous tumor mouse model of CRC, TPST-1495 decreased tumor size and number of tumors. Immunohistochemistry analysis of the resected small intestine tumors revealed increased immune infiltrate and an enhanced adaptive immune transcriptional profile.