On November 12, 2021 InterVenn Biosciences, the leader in glycoproteomics, reported on a predictive signature capable of identifying non-small cell lung cancer patients that will benefit most from immune checkpoint inhibitors (Press release, InterVenn Biosciences, NOV 12, 2021, View Source [SID1234595480]). This signature was developed using InterVenn’s perspectIV platform which combines high-resolution mass-spectrometry-derived glycoprotein profiling with advanced artificial intelligence and neural-networking-based data processing to newly allow glycoproteomic interrogation at clinical scale, opening up a revolutionary, highly powerful new layer of biomarker opportunities.

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An oral presentation today at the Conference for the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) outlined the results of a study whereby pre-treatment blood samples from a cohort of patients treated with first-line pembrolizumab (alone or in combination with chemotherapy) were interrogated using the perspectIV platform. A panel of glycopeptide markers predictive of response was identified. This glycopeptide-based signature stratified the patient cohort into two groups which showed significant differences in median overall survival of 2.8 years vs. 0.8 years, at a hazard ratio of 7.4, (p=0.007).

"These results are an important step in the development of our Dawn assay and were the impetus of our current development and validation activities," said Aldo Carrascoso, CEO and co-founder of InterVenn. "We look forward to sharing the results of our current development and validation efforts in NSCLC and other indications as we proceed to the launch of Dawn in 2022."

To find out more about InterVenn Biosciences or partnership opportunities, visit View Source

On November 12, 2021 Moderna, Inc., (Nasdaq: MRNA) a clinical-stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, reported interim data from an ongoing Phase 1 clinical study of mRNA-2752 (Triplet) in patients with accessible solid tumors and lymphomas (Press release, Moderna Therapeutics, NOV 12, 2021, View Source [SID1234595479]). The data showed that the Company’s mRNA Triplet program given in combination with AstraZeneca’s durvalumab (IMFINZI) was tolerated at all dose levels tested and elicited evidence of anti-tumor activity. The recommended dose for expansion (RDE) is up to of 8mg mRNA-2752 + durvalumab.

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"We are encouraged by the interim data from our Triplet program, which combines three mRNAs into one therapy injected directly into the tumor. Our intratumoral mRNA technology allows for the delivery of mRNAs encoding for multiple proteins that act locally to modulate the tumor microenvironment, without systemic toxicity," said Praveen Aanur, M.D., Vice President, Therapeutic Area Head for Oncology Development at Moderna. "These interim results demonstrate the potential role of immune modulation on clinical outcomes and we look forward to full results from the dose expansion arm of the study."

Presented today at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting, the study demonstrates evidence of immunomodulation and expected pharmacodynamics in the tumour immune microenvironment (TME) of both injected and un-injected lesions, in both monotherapy and combination cases, as indicated by increases in proliferating (activated) T cells, PD-L1 levels (marker of interferon signaling), and T cell-inflamed (GEP) and DC transcriptional signature score, with greatest changes observed in patients with clinical benefit.

This Phase 1 open-label, multicenter, dose-escalation study is evaluating the safety and tolerability of escalating intratumoral injections of mRNA-2752 alone and in combination with PD-L1 inhibitor (durvalumab) to define the maximum tolerated dose (MTD) or a recommended dose for expansion (RDE). The study consists of dose escalation and dose confirmation parts, which will occur in Arm A and Arm B, followed by a dose expansion part, which will occur in Arm B, and a Dose Exploration in Arm C as a neoadjuvant therapy for cutaneous melanoma. The Company presented the interim results of Part A at the 2020 ASCO (Free ASCO Whitepaper) Annual Meeting. Enrollment in dose expansion part of Arm B and Arm C is currently ongoing.

Moderna’s mRNA technology enables novel combination of targets. mRNA-2752 consists of three mRNAs which encode for different proteins including OX40 ligand, a T-cell costimulatory protein, which can enhance expansion and survival of both CD4 and CD8 T cells; and two cytokines, IL-23, a pro-inflammatory cytokine of the IL-12 family, which can cause priming of dendritic cells and also activation of other immune cells; and IL-36γ, a pro-inflammatory cytokine of IL-1 family, which can help in the maturation of dendritic cells.

About the Data

Abstract 529: Phase 1 Study of mRNA-2752, a Lipid Nanoparticle Encapsulating mRNAs Encoding huOX40L, IL-23, and IL-36γ Intratumoral (iTu) Injection +/- Durvalumab in Advanced Solid Tumors and Lymphoma

The SITC (Free SITC Whitepaper) poster is now available on the "Events and Presentations" section of the Moderna website.

In Arm B of this dose-escalation study, 32 patients with accessible solid tumors and lymphomas received mRNA-2752 in combination with intravenously administered immune checkpoint blockade therapy (durvalumab).

Results:

iTu mRNA-2752 given as monotherapy and in combination with durvalumab is tolerable at all dose levels studied; the recommended dose for expansion (RDE) is up to 8mg mRNA-2752 + durvalumab

Median IL-23 plasma levels maintained at < 1ng/mL with dose ranges up to 8mg supports the therapeutic goal of ITu therapy to limit systemic exposure and toxicity

Administration of iTu mRNA-2752 is associated with tumor shrinkage in both injected and un-injected lesions as monotherapy and in combination with durvalumab

Durable PRs seen in a PD-L1-low squamous-cell bladder cancer patient, and a Diffuse large B-cell lymphoma (DLBCL) after progression on CAR-T

Treatment response of the injected lesion was seen in a melanoma patient progressed on pembrolizumab and T-VEC

Evidence of immunomodulation/ expected pharmacodynamics in the TME of both injected and un-injected lesions, in both monotherapy and combination cases, as indicated by increases in proliferating (activated) T cells, PD-L1 levels (marker of interferon signaling), and T cell-inflamed (GEP) and DC transcriptional signature score, with greatest changes observed in patients with clinical benefit

Pro-inflammatory cytokines, including IFN-γ, are predominantly transiently elevated post- monotherapy treatment, peaking at 24 hours post-treatment; trend toward further elevated levels of a subset of cytokines, including TNF-α, in combination with durvalumab

PK/PD modeling supports QW dosing which is being explored in cutaneous melanoma in the neoadjuvant setting

Enrollment is ongoing in expansion cohorts of triple-negative breast cancer (TNBC), urothelial carcinoma, lymphoma, and immune checkpoint refractory melanoma and n on-small cell lung cancer (NSCLC)
About Moderna’s Immuno-Oncology Programs

Moderna’s oncology programs are currently focused on two main areas: cancer vaccines and intratumoral immuno-oncology (I/O) therapies. Moderna is developing these potential mRNA treatments as monotherapies and/or in combination with checkpoint inhibitors from our strategic collaborators Merck and AstraZeneca.

An advantage of Moderna’s mRNA platform is that it allows for investigational medicines that combine in a single mRNA therapy several different approaches to activate the immune system to attack cancer, either with mRNA encoding for common tumor proteins found across cancer types or multiple mRNAs encoding for various immunomodulatory proteins.

On November 12, 2021 Humanigen, Inc. (Nasdaq: HGEN) (Humanigen), a clinical stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‛cytokine storm’ with its lead drug candidate, lenzilumab, reported financial results for the third quarter and nine months ended September 30, 2021 (Press release, Humanigen, NOV 12, 2021, View Source [SID1234595478]).

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Status of Application to UK’s Medicines and Healthcare Products Regulatory Agency (MHRA)

On June 11, 2021, Humanigen initiated submission of an application seeking Conditional Marketing Authorization (CMA) from the UK’s MHRA for lenzilumab in hospitalized COVID-19 patients and it was accepted for expedited COVID-related rolling review on July 9, 2021. Humanigen submitted the last of the planned modules on September 30, 2021. The company believes MHRA is actively reviewing its application.

"We are continuing our efforts to get lenzilumab to hospitalized COVID-19 patients. The recent selection of lenzilumab by the European Commission as one of the 10 most promising treatments for COVID-19, validates our view that lenzilumab offers meaningful clinical potential.1 We appreciate the commitment MHRA has made to reviewing our application," said Cameron Durrant, Chairman and CEO, Humanigen. "The vaccination rate in the UK is 79%, yet hospitalizations due to COVID-19 continue. We continue to work with regulators in the UK, US, and European Union to potentially bring this therapy to patients."2

Recent data suggests that the protection offered to fully vaccinated individuals from infection and severe disease wanes over time and there is a continued need for additional treatment options for patients who become severely ill after infection with SARS-CoV-2.3 Despite nearly 80% of the population in the UK being fully vaccinated, there were nearly 25,000 COVID-19 patients newly admitted to hospitals for treatment in October, more than 60% of whom were fully vaccinated. 2,4,5

Timothy Morris, COO/CFO, Humanigen, noted, "We are preparing for potential launch in the UK if lenzilumab were to receive authorization from MHRA by securing a supply chain to import, release and distribute lenzilumab to UK hospitals. Separately, our agreement with Clinigen, once fully operational, will allow us to distribute lenzilumab to patients in 16 countries in the EU where regulations allow for managed access, named patient, compassionate use or similar programs. We are also pleased by the progress being made to evaluate lenzilumab in Chronic Myelomonocytic Leukemia (CMML), acute Graft versus Host Disease (aGvHD), and our own effort to conduct a Phase 3 study with commercially-approved CD19 CAR-T therapies in non-Hodgkin lymphoma (NHL)."

Third Quarter and Recent Highlights:

Lenzilumab in hospitalized COVID-19

European Commission selected Humanigen’s lenzilumab as one of the 10 most promising treatments for COVID-19.
Submitted final required modules as well as a risk management plan and pediatric investigation plan for CMA for lenzilumab in COVID-19 to the UK’s MHRA.
EMA appointed a Rapporteur and Co-Rapporteur related to the company’s planned submission of an MAA for lenzilumab in COVID-19 in the EU.
Entered into agreement with Clinigen Group to establish a Managed Access Program to enable access to lenzilumab on a case-by-case basis to patients in up to 16 European countries.
Requested and granted a Type B meeting with FDA. Included in the briefing materials for the meeting request were day 60 data as well as detailed CRP analysis from the company’s LIVE-AIR Phase 3 study.
Lenzilumab in CMML, aGvHD, and NHL

First patient dosed in Phase 2 study of lenzilumab in patients with Chronic Myelomonocytic Leukemia (CMML), sponsored by the company’s Australian partners.
Reached agreement with University of Birmingham to conduct a Phase 2/3, potentially registrational, trial to evaluate lenzilumab in the treatment of aGvHD at IMPACT Partnership stem cell transplant centers across the UK.
Scheduled a meeting in December 2021 with FDA to discuss a protocol to conduct a Phase 3 randomized, placebo-controlled, open-label trial of lenzilumab to improve the safety and efficacy of CD19 CAR-T therapies in the treatment of NHL.
Corporate

Elected John Hohneker, MD, and Kevin Xie, PhD, to Board of Directors.
Received U.S. Patent 11,130,805 protecting the method of treating CAR-T cell therapy-induced neurotoxicity using a GM-CSF inhibitor. The patent issued on September 28, 2021 and has an expected patent term through October 2, 2038.
ACTIV-5 Update

In August 2021, the National Institutes of Health (NIH) announced the advancement of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-5) and Big Effect Trial, in the "B" arm of the trial (BET-B), referred to as ACTIV-5/BET-B. Following feedback from and consultation with the company, the NIH advanced the study to a Phase 2/3 study with target enrollment of up to 400 patients with a baseline CRP<150 mg/L, or a total of up to 550 patients, and amended the protocol for ACTIV-5/BET-B in a manner that aligns with the design of the company’s LIVE-AIR trial. The trial is approximately 75% enrolled.

Third Quarter and Nine Months Ended September 30, 2021 Financial Results

Net loss for the three months ended September 30, 2021 was $66.7 million or $1.12 per share as compared to $30.8 million or $0.71 per share for the three months ended September 30, 2020. The net loss for the nine months ended September 30, 2021 was $203.1 million or $3.56 per share as compared to $57.2 million or $1.79 per share for the nine months ended September 30, 2020. The increase in net loss for both periods was largely due to an increase in total expenses, mainly Research and Development ("R&D") expense which rose significantly as the company accelerated its efforts to manufacture lenzilumab for potential commercialization upon receipt of a regulatory authorization. R&D expense increased $38.4 million from $22.4 million for the three months ended September 30, 2020, to $60.8 million for the three months ended September 30, 2021, and increased $139.6 million from $44.2 million for the nine months ended September 30, 2020, to $183.8 million for the nine months ended September 30, 2021. The manufacturing expense included in R&D was $55.8 million for the third quarter of 2021 as compared to $10.9 million for the prior year quarter, and $162.9 million for the nine months ended September 30, 2021, as compared to $28.3 million for the prior year period. Manufacturing expense is comprised of technical transfer, start-up and production expenses for bulk drug substance (BDS) and drug product (DP). The company has built an extensive network of contract manufacturing organizations (CMOs) to produce lenzilumab BDS, to fill DP, and to establish a supply chain for lenzilumab.

On September 8, 2021, FDA declined the company’s Emergency Use Authorization (EUA) request for lenzilumab in hospitalized COVID-19 patients. Subsequently, the company has amended, and in some cases canceled, certain of its manufacturing agreements, some of which were contingent on EUA, in an effort to reduce its future spending on lenzilumab production until and if authorization is received in the UK, EU, or US. In the event of authorization by MHRA, EMA, or FDA, the company anticipates that the demand for commercial product could exceed the in process and planned production of lenzilumab through 2022. The company intends to seek additional manufacturing capacity if authorization is obtained. Production beyond 2022 would require the company to secure capacity at our CMOs and acquire the necessary supplies and components. The Company expects to use a portion of the revenues generated from commercial sale of lenzilumab following receipt of a regulatory authorization to support its efforts to expand production capacity in 2023 and beyond.

Certain of the company’s CMOs have been unsuccessful in their efforts to manufacture some batches of lenzilumab to the company’s specifications for various reasons. The company is working with these CMOs to determine if batches of BDS manufactured by them may be usable in the future or, if not, whether other financial recompense will be offered to the company.

Cash and Cash Equivalents

Net cash used in operating activities, net of balance sheet changes, was $48.0 million for the three months ended September 30, 2021, and $151.8 million for the nine months ended September 30, 2021. During the nine months ended September 30, 2021, the company raised net proceeds of $40.0 million from the sale of shares of common stock under its At-the-Market offering program, drew $25.0 million under its credit facility with Hercules Capital, providing net proceeds of $24.4 million, and completed a public offering of common stock with net proceeds of $94.2 million. As of September 30, 2021, the company had cash and cash equivalents of $76.5 million. Subsequent to September 30, 2021, the company received net proceeds of approximately $24.5 million under its At-the-Market offering program.

A summary of key financial highlights as of and for the three and nine months ended September 30, 2021 and 2020 is as follows ($ in thousands):

On November 12, 2021 Treadwell Therapeutics, a clinical-stage biotechnology company developing novel medicines for highly aggressive cancers, reported a presentation for the Company’s CFI-402411 program, an oral, first-in-class inhibitor of Hematopoietic Progenitor Kinase 1 (HPK1) a negative regulator of immune cell activation, at the 36th Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting being held virtually and in-person from November 10-14, 2021 at the Walter E. Washington Convention Center in Washington, D.C (Press release, Treadwell Therapeutics, NOV 12, 2021, View Source [SID1234595477]). This presentation will describe preliminary dose escalation data from TWT-101, a Treadwell-sponsored, first in human study of CFI-402411 in advanced solid tumors.

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"CFI-402411 is a potent, orally available small molecule inhibitor of HPK1 (Hematopoietic progenitor kinase 1, also known as mitogen activated protein kinase kinase kinase kinase 1, MAP4K1). HPK1 is a negative regulator of both T and B cell responses. We have seen preliminary indications of tolerability and clinical benefit in patients with multiple solid tumors, including post PD1 progression" said Dr. Omid Hamid, Chief of Research/ Immuno-Oncology at The Angeles Clinic & Research Institute, a Cedars-Sinai affiliate, Los Angeles, California.

"HPK1 inhibition with CFI-402411 represents a novel means to stimulate anti-tumor immunity, through an orally available therapy," said Dr. Michael Tusche, co-Chief Executive Officer at Treadwell Therapeutics. "As the first HPK1 inhibitor in the clinic, we are excited by the promise of CFI-402411 and look forward to sharing additional results from TWT-101, including pembrolizumab combination and biomarker focused cohorts, throughout 2022 and beyond."

2021 SITC (Free SITC Whitepaper) Poster Presentations and Details:

TWT-101: A First In-human, Phase 1/2 Study Of CFI-402411, Hematopoietic Progenitor Kinase-1 (HPK1) Inhibitor, As A Single Agent And In Combination With Pembrolizumab In Subjects With Advanced Solid Malignancies
Publication Number: 489
Poster Hall
Date and Time: November 12, 2021, 7:00 am – 8:30 pm

In the presentation titled, "TWT-101: A First In-human, Phase 1/2 Study of CFI-402411, Hematopoietic Progenitor Kinase-1 (HPK1) Inhibitor, as a single agent and in combination with pembrolizumab in subjects with advanced solid malignancies," CFI-402411 demonstrated a tolerable safety profile at doses up to 400 mg qd, linear pharmacokinetics, and biologically effective concentrations in patients, as assessed by an exploratory in vitro SLP-76 assay. In this heavily pre-treated, all-comer patient population (N=16), 5 patients achieved stable disease as best response for at least one tumor evaluation, with 2 of those patients (salivary gland and basal cell carcinoma) exhibiting stable disease through at least 3 tumor evaluations. The basal cell carcinoma patient had been previously treated with anti-PD1 antibodies. The most common drug related toxicities of any grade, which occurred in greater than 10% of patients, were diarrhea (62.5%), nausea (43.8%), decreased appetite (31.3%), dyspepsia (25%), blood creatinine increase (25%), and fatigue (25%).

About CFI-402411

CFI-402411 is a highly potent inhibitor of HPK1, which in preclinical studies has been shown to have an immune-activating effect including the alleviation of inhibition of T cell receptors (TCR), disruption of abnormal cytokine expression, alteration of the tumor immunosuppressive environment through effector cells (i.e. Regulatory T cells or Treg), and potent anti-leukemic effects in several mouse models.

About TWT-101

TWT-101 is a Phase 1/2 clinical trial of CFI-402411 in advanced solid malignancies. The study is designed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of CFI-402411, as well as to determine optimal dosing as a monotherapy and in combination with the anti-PD1 antibody, pembrolizumab. The trial will enroll approximately 170 patients at up to 15 sites in North America and Asia. It will involve 5 arms including monotherapy and combination dose escalation and expansion in a variety of tumor types, as well as biomarker backfills

On November 12, 2021 MingSight Pharmaceuticals reported the close of a pre-Series B round of $20M, led by Kaitai Capital (Press release, MingSight Pharmaceuticals, NOV 12, 2021, View Source [SID1234595475]). The proceeds will be used for the clinical development of MS-553, a new generation inhibitor of protein kinase C (PKC) beta for the treatment of Chronic lymphocytic Leukemia (CLL) and Diabetic Macular Edema (DME).

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"We greatly appreciate the trust and support of our investors," said Kai Zhang, MD, MBA, CEO and Co-founder of MingSight. "This investment will facilitate the rapid development of the MS-553 program. We are very excited to see MS-553 demonstrate strong efficacy and safety data in our CLL and DME trials. We will work hard to bring forward a truly differentiated product to market to improve upon the treatment options for these serious diseases."

Michael Niesman, Ph.D., CSO and Co-founder of MingSight, said: "We are very glad that our investors share our excitement about the promise of MS-553. Many companies have been convinced of the importance of Protein Kinase C (PKC) in serious diseases like CLL and diabetic eye disease. Because of the major innovations of MS-553 compared to previous pan-PKC inhibitors, we have been able to generate data demonstrating proof of mechanism and significant activity in CLL and DME where other PKC inhibitors have failed. We look forward to working with Kaitai and our other investors to accelerate the development of this unique compound."

Zehua Huang, Partner at Kaitai Capital, said: "We believe MingSight has a world class team and advisory group, and its program is well positioned for the future marketplace. With initial efficacy in CLL patients with C481S and PLCG2 mutations, MS-553 showed distinct promise of its market potential. MS-553 has the potential to improve upon the standard of care therapies for CLL as a single agent or in combination with BTK inhibitors, BCL-2 inhibitors, or other agents. As for its application in DME treatment, MS-553 has the potential to provide an alternative, non-invasive approach to ocular injections of anti-VEGF agents. A key characteristic of MS-553 is its preferential distribution to the retina following oral administration. The initial clinical data of MS-553 in DME patients such as BCVA and CRT readings are very impressive. We are confident that MingSight will succeed in rapidly developing MS-553 and bringing its benefits to patients worldwide."

About MS-553

MS-553 is an investigational drug candidate and a new generation PKC beta inhibitor. It differentiates from the previous generation of pan-PKC inhibitors with its novel chemotype and significant advantages in selectivity, safety, and PK properties.

MS-553 is a potentially the only B-cell receptor inhibitor in clinical development that can address the BTK resistant mutations in both BTK and PLCG2. Its mechanism of action is also synergistic or additive to other approaches that constitute the current standard of care of CLL.

MS-553 also has the potential, if approved, to become the first oral DME therapy with anti-VEGF like efficacy. MS-553 has the unique PK property of preferential distribution to the retina and its mechanism of action addresses both the aberrant VEGF signaling and the inflammation that are characteristics of DME.

In a phase 1/2 study, MS-553 demonstrated promising efficacy and safety in CLL patients who have failed BTK inhibitors including those with C481S and PLCG2 resistant mutations. MS-553 also demonstrated clinical activities including reduction of retinal thickness and improvement of visual acuity in a phase 1b trial of DME patients.