On May 16, 2022 Terns Pharmaceuticals, Inc. ("Terns" or the "Company") (Nasdaq: TERN), a clinical-stage biopharmaceutical company developing a portfolio of small-molecule single-agent and combination therapy candidates to address serious diseases such as non-alcoholic steatohepatitis (NASH), obesity and cancer, reported financial results for the first quarter ended March 31, 2022 and business updates (Press release, Terns Pharmaceuticals, MAY 16, 2022, View Source [SID1234614641]).

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"The Terns team has continued to advance our pipeline with the opening of our combination therapy IND for NASH and the commencement of key IND-enabling activities in our GLP-1 program in obesity, along with the initiation of a clinical trial for TERN-701 in chronic myeloid leukemia by Hansoh, our development partner in China," said Senthil Sundaram, chief executive officer at Terns. "As we continue this momentum across our diverse pipeline, we remain committed to a prudent approach to funding our operations. Following a strategic review of our pipeline, we have decided to focus our resources on advancing our most promising pipeline candidates: (1) TERN-501, including combination therapy development with TERN-101, (2) TERN-601, our oral, small-molecule GLP-1 candidate, and (3) supporting our partner’s clinical development of TERN-701 for CML in China. This decision extends our expected cash runway into 2025, enabling key expected clinical trial readouts across three indications for TERN-501, TERN-601, and TERN-701 during that time period."

Recent Developments and Anticipated Milestones

TERN-501: Thyroid hormone receptor-beta (THR-β) agonist for NASH

TERN-501 is a THR-β agonist with high metabolic stability, enhanced liver distribution and greater selectivity for THR-β compared to other THR-β agonists in development
Investigational new drug (IND) application for Terns’ NASH combination therapy program was opened in April 2022, supporting the planned Phase 2a clinical trial of TERN-501 as monotherapy and in combination with TERN-101 (Terns’ liver-distributed farnesoid X receptor (FXR) agonist), as well as future studies of other combination therapy regimens
The Phase 2a trial is a multicenter, randomized, double-blind, placebo-controlled clinical trial in noncirrhotic NASH patients using a factorial design including both monotherapy and combination arms of TERN-501 and TERN-101
The trial is expected to enroll approximately 140 adult patients with elevated body mass index (BMI ≥ 25 kg/m2) and NASH with fibrosis, but not cirrhosis, based on prior liver biopsy and/or imaging and clinical criteria
All patients must have liver fat content measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF) of ≥10%, MRI corrected T1 (cT1) relaxation time of ≥ 800 msec, and meet other inclusion and exclusion criteria
The trial includes a 12-week treatment period and a 4-week follow-up period
The primary endpoint will be the relative change from baseline in MRI-PDFF at Week 12 for TERN-501 monotherapy compared with placebo
Secondary endpoints include assessment of changes in MRI-PDFF (combination vs. placebo) and cT1 (TERN-501 monotherapy vs. placebo as well as 501+101 combination vs. placebo)
IND has been opened in the United States; Phase 2a trial has been initiated with screening expected to start in June 2022, and top-line data expected in the second half of 2023
TERN-601: Oral, small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist for obesity

TERN-601 is an oral small-molecule glucagon-like peptide-1 receptor, or GLP-1R, agonist for the treatment of obesity
Terns screened more than 20,000 molecular permutations through its proprietary quantitative structure activity relationship (QSAR) model to identify suitable small-molecule scaffolds with potentially improved properties relative to other GLP-1-based approaches
Terns has identified structures believed to be suitable for oral administration as a single-agent or in combination with other drug candidates within its pipeline
IND-enabling activities for TERN-601, Terns’ lead GLP-1R development candidate, are underway with the goal of initiating a first-in-human clinical trial in 2023
The Phase 1 clinical program for TERN-601 is expected to include a single ascending dose trial in healthy volunteers and a multiple ascending dose proof-of-concept trial assessing potential endpoints such as body weight and HbA1c
TERN-701: Oral, allosteric BCR-ABL tyrosine kinase inhibitor (TKI) for chronic myeloid leukemia

TERN-701 is Terns’ proprietary, allosteric BCR-ABL TKI, designed to target the ABL myristoyl pocket, which is in development for the treatment of chronic myeloid leukemia (CML), a form of cancer that begins in the bone marrow
TERN-701 was designed with the goal of achieving improved tumor suppression against a broader range of mutations, an enhanced pharmacokinetic profile with an increased half-life and simplified dosing compared to the only available allosteric BCR-ABL TKI, recently approved by the FDA
TERN-701 is out-licensed to Hansoh Pharmaceutical Group Company Limited for development in the greater China region (referred to as HS-10382 by Hansoh); Terns retains all worldwide development and commercialization rights outside of greater China, as well as access to data generated by Hansoh in China
A Phase 1 trial of TERN-701 in CML patients in China has been initiated by Hansoh, with patient dosing currently underway; Hansoh is responsible for all development and commercialization-related activities in greater China
Terns plans to explore options for the development and commercialization of TERN-701 outside of greater China, including additional strategic partnerships
TERN-201: Vascular adhesion protein-1 (VAP-1) inhibitor

Terns reported top-line results from Part 1 of the Phase 1b AVIATION Trial in March 2022
Part 1 of the AVIATION Trial met the primary safety endpoint: TERN-201 10 mg administered once daily to NASH patients was generally safe and well-tolerated with no meaningful changes in exploratory serum or imaging NASH biomarkers, including cT1
Further spend for TERN-201 in NASH has primarily been limited to the completion of Part 2 (20 mg dose) of the ongoing AVIATION Trial with results expected in 4Q 2022; Terns plans to evaluate all AVIATION data at that point to inform next steps for clinical development in NASH or other indications where VAP-1 is implicated
Business Update

Terns completed a proactive and financially disciplined review of the Company’s operations, resulting in the prioritization of resources towards development activities related to TERN-501 (including the planned Phase 2a clinical trial of TERN-501 as monotherapy and in combination with TERN-101) and the GLP-1R agonist program, including TERN-601, and supporting Hansoh’s clinical development of TERN-701 for CML in China
As a result of these decisions, Terns anticipates existing cash to be sufficient to fund operations into 2025, including three expected clinical trial readouts for three product candidates across three indications during that time period
Upcoming Investor Events

Terns will present at the UBS Global Healthcare Conference on Monday, May 23, 2022 at 8:30am ET. A live webcast of the event will be available on the investor relations page of the Terns Pharmaceuticals website at View Source A replay of the webcast will be archived on Terns’ website for 30 days following the presentation
First Quarter 2022 Financial Results

Cash Position: As of March 31, 2022, cash, cash equivalents and marketable securities were $151.3 million, as compared with $166.0 million as of December 31, 2021. Based on its current operating plan, Terns expects these funds will be sufficient to support its planned operating expenses into 2025.
Research and Development (R&D) Expenses: R&D expenses were $8.1 million for the quarter ended March 31, 2022, as compared with $8.7 million for the quarter ended March 31, 2021.
General and Administrative (G&A) Expenses: G&A expenses were $5.7 million for the quarter ended March 31, 2022, as compared with $4.6 million for the quarter ended March 31, 2021.
Net Loss: Net loss was $13.8 million for the quarter ended March 31, 2022, as compared with $13.3 million for the quarter ended March 31, 2021.

On May 16, 2022 Pfizer Inc. (NYSE: PFE, "Pfizer") and BioNTech SE (Nasdaq: BNTX, "BioNTech") reported they have reached an agreement with the European Commission (EC) to amend their originally agreed contractual delivery schedules for the Pfizer-BioNTech COVID-19 Vaccine (Press release, BioNTech, MAY 16, 2022, View Source [SID1234614657]). This amendment rephases planned deliveries to help support the European Commission and Member States’ ongoing immunization programs, and is aligned to the companies’ commitment to working collaboratively to identify pragmatic solutions to address the evolving pandemic needs. Doses scheduled for delivery in June through August 2022 will now be delivered in September through fourth quarter 2022. The companies’ full-year 2022 revenue guidance and the full-year commitment of doses to be delivered to EC Member States in 2022 remain unchanged.

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Pfizer and BioNTech continue to evaluate potential adapted vaccines, including variant-based vaccines.

U.S. Indication & Authorized Use

Pfizer-BioNTech COVID-19 Vaccine is FDA authorized under Emergency Use Authorization (EUA) for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 5 years of age and older.

Pfizer-BioNTech COVID-19 Vaccine is FDA authorized to provide:

Primary Series

a 2-dose primary series to individuals 5 years of age and older
a third primary series dose to individuals 5 years of age and older with certain kinds of immunocompromise
Booster Series

a first booster dose to individuals 12 years of age and older who have completed a primary series with Pfizer-BioNTech COVID-19 Vaccine or COMIRNATY (COVID-19 Vaccine, mRNA)
a first booster dose to individuals 18 years of age and older who have completed primary vaccination with a different authorized or approved COVID-19 vaccine. The booster schedule is based on the labeling information of the vaccine used for the primary series
a second booster dose to individuals 50 years of age and older who have received a first booster dose of any authorized or approved COVID-19 vaccine
a second booster dose to individuals 12 years of age and older with certain kinds of immunocompromise and who have received a first booster dose of any authorized or approved COVID-19 vaccine
COMIRNATYINDICATION

COMIRNATY (COVID-19 Vaccine, mRNA) is a vaccine approved for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 16 years of age and older.

COMIRNATY is administered as a 2-dose primary series
COMIRNATY AUTHORIZED USES

COMIRNATY (COVID-19 Vaccine, mRNA) is FDA authorized under Emergency Use Authorization (EUA) to provide:

Primary Series

a 2-dose primary series to individuals 12 through 15 years of age
a third primary series dose to individuals 12 years of age and older with certain kinds of immunocompromise
Booster Dose

a first booster dose to individuals 12 years of age and older who have completed a primary series with Pfizer-BioNTech COVID-19 Vaccine or COMIRNATY
a first booster dose to individuals 18 years of age and older who have completed primary vaccination with another authorized or approved COVID-19 vaccine. The booster schedule is based on the labeling information of the vaccine used for the primary series
a second booster dose to individuals 50 years of age and older who have received a first booster dose of any authorized or approved COVID-19 vaccine
a second booster dose to individuals 12 years of age and older with certain kinds of immunocompromise and who have received a first booster dose of any authorized or approved COVID-19 vaccine

Emergency Use Authorization

Emergency uses of the vaccine have not been approved or licensed by FDA, but have been authorized by FDA, under an Emergency Use Authorization (EUA) to prevent Coronavirus Disease 2019 (COVID 19) in either individuals 12 years of age and older, or in individuals 5 through 11 years of age, as appropriate. The emergency uses are only authorized for the duration of the declaration that circumstances exist justifying the authorization of emergency use of the medical product under Section 564(b)(1) of the FD&C Act unless the declaration is terminated or authorization revoked sooner.

INTERCHANGEABILITY

FDA-approved COMIRNATY (COVID-19 Vaccine, mRNA) and the Pfizer-BioNTech COVID-19 Vaccine FDA-authorized for Emergency Use Authorization (EUA) for individuals 12 years of age and older can be used interchangeably by a vaccination provider when prepared according to their respective instructions for use.

The formulation of the Pfizer-BioNTech COVID-19 Vaccine authorized for use in children 5 through 11 years of age differs from the formulations authorized for individuals 12 years of age and older and should therefore not be used interchangeably. The Pfizer-BioNTech COVID-19 Vaccine authorized for use in children 5 through 11 years of age should not be used interchangeably with COMIRNATY (COVID-19 Vaccine, mRNA).

IMPORTANT SAFETY INFORMATION

Tell your vaccination provider about all of your medical conditions, including if you:

have any allergies
have had myocarditis (inflammation of the heart muscle) or pericarditis (inflammation of the lining outside the heart)
have a fever
have a bleeding disorder or are on a blood thinner
are immunocompromised or are on a medicine that affects the immune system
are pregnant, plan to become pregnant, or are breastfeeding
have received another COVID-19 vaccine
have ever fainted in association with an injection
Pfizer-BioNTech COVID-19 Vaccine or COMIRNATY (COVID-19 Vaccine, mRNA) may not protect all vaccine recipients
You should not receive Pfizer-BioNTech COVID-19 Vaccine or COMIRNATY (COVID-19 Vaccine, mRNA) if you have had a severe allergic reaction to any of its ingredients or had a severe allergic reaction to a previous dose of Pfizer-BioNTech COVID-19 Vaccine or COMIRNATY
There is a remote chance that Pfizer-BioNTech COVID-19 Vaccine or COMIRNATY (COVID-19 Vaccine, mRNA) could cause a severe allergic A severe allergic reaction would usually occur within a few minutes to 1 hour after getting a dose of the vaccine. For this reason, your vaccination provider may ask you to stay at the place where you received the vaccine for monitoring after vaccination. If you experience a severe allergic reaction, call 9-1-1 or go to the nearest hospital
Seek medical attention right away if you have any of the following symptoms:

difficulty breathing, swelling of the face and throat, a fast heartbeat, a bad rash all over the body, dizziness, and weakness
Myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the lining outside the heart) have occurred in some people who have received the vaccine, more commonly in males under 40 years of age than among females and older males. In most of these people, symptoms began within a few days following receipt of the second dose of the vaccine. The chance of having this occur is very low
Seek medical attention right away if you have any of the following symptoms after receiving the vaccine:

chest pain
shortness of breath
feelings of having a fast-beating, fluttering, or pounding heart
Fainting can happen after getting injectable vaccines, including Pfizer-BioNTech COVID-19 Vaccine or COMIRNATY (COVID-19 Vaccine, mRNA). Sometimes people who faint can fall and hurt themselves. For this reason, your vaccination provider may ask you to sit or lie down for 15 minutes after receiving the vaccine
Some people with weakened immune systems may have reduced immune responses to Pfizer-BioNTech COVID-19 Vaccine or COMIRNATY (COVID-19 Vaccine, mRNA)
Additional side effects include injection site pain; tiredness; headache; muscle pain; chills; joint pain; fever; injection site swelling; injection site redness; nausea; feeling unwell; swollen lymph nodes (lymphadenopathy); decreased appetite; diarrhea; vomiting; arm pain; and fainting in association with injection of the vaccine
These may not be all the possible side effects of the vaccine. Call the vaccination provider or healthcare provider about bothersome side effects or side effects that do not go away.

You should always ask your healthcare providers for medical advice about adverse events. Report vaccine side effects to the US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) Vaccine Adverse Event Reporting System (VAERS). The VAERS toll-free number is 1‐800‐822‐7967 or report online to www.vaers.hhs.gov/reportevent.html. You can also report side effects to Pfizer Inc. at www.pfizersafetyreporting.com or by calling 1-800-438-1985

On May 16, 2022 ITM Isotope Technologies Munich SE (ITM), a leading radiopharmaceutical biotech company, reported that it will host a scientific symposium on precision oncology titled "Targeted Radionuclide Therapy – present and future prospects" held as an ancillary event in parallel to the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting (Press release, ITM Isotopen Technologien Munchen, MAY 16, 2022, View Source [SID1234614673]). The symposium will feature key opinion leaders in the field and will be held in a hybrid format on June 03, 2022 from 11:00 am – 12:30 pm CST in the Hyatt Regency McCormick Place, in Chicago, USA and online.

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Targeted Radionuclide Therapy is an approach to treating a variety of cancer types. As new areas of interest and advancing approaches to implementing this uniquely selective therapeutic modality continue to be highlighted, the session will offer an overview of the key topics. The panel will focus on the clinical application of Targeted Radionuclide Therapy in the treatment of neuroendocrine tumors, prostate cancer and potential future prospects. They will also spotlight the benefits and risks of this therapeutic approach, address any challenges that may be encountered, and provide valuable insights to their patient management experiences. Participants will be able to interact with the speakers in a Q&A session at the end of the event.

Scientific Program and Speakers:

Welcome and Introduction
Pamela Kunz, MD
Smilow Cancer Hospital and Yale Cancer Center

Clinical Application of Targeted Radionuclide Therapy in Neuroendocrine Tumors
Pamela Kunz, MD (20min)
Smilow Cancer Hospital and Yale Cancer Center, New Haven

Clinical Application of Targeted Radionuclide Therapy in Prostate Cancer
Michael Morris, MD (20 min)
Memorial Sloan Kettering Cancer Center, New York

Personalizing the Targeted Radionuclide Therapy, Advancements and Challenges
Thomas Hope, MD (20min)
University of California, San Francisco

The Future of Targeted Radionuclide Therapy
Wolfgang Weber, MD, PhD (20min)
Klinikum rechts der Isar (the University Hospital of the Technical University of Munich)

Discussion & Closing Remarks
Pamela Kunz, MD

For the full scientific program and registration form please click here:
View Source

The symposium will be recorded, and available on demand for 6 months after the event.

The event is not sponsored, endorsed, or accredited by ASCO (Free ASCO Whitepaper), CancerLinQ, or Conquer Cancer the ASCO (Free ASCO Whitepaper) Foundation.

About Targeted Radionuclide Therapy

Targeted Radionuclide Therapy is an emerging class of cancer therapeutics, which seeks to deliver radiation directly to the tumor while minimizing radiation exposure to normal tissue. Targeted radiopharmaceuticals are created by linking a therapeutic radioisotope to a targeting molecule (e.g., peptide, antibody, small molecule) that can precisely recognize tumor cells and bind to tumor-specific characteristics, like receptors on the tumor cell surface. As a result, the radioisotope accumulates at the tumor site and decays, releasing a small amount of ionizing radiation, thereby destroying tumor tissue. The highly precise localization enables targeted treatment with minimal impact to healthy surrounding tissue.

On May 16, 2022 Adaptimmune Therapeutics plc (Nasdaq: ADAP), a leader in cell therapy to treat cancer, reported that it is presenting preclinical proof-of-concept data from its second next-generation SPEAR T-cell (ADP-A2M4N7X19) targeting MAGE-A4, and novel tumor-infiltrating lymphocytes (TILs) expressing IL-7 (ADP-TILIL7) at the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) annual meeting (Press release, Adaptimmune, MAY 16, 2022, View Source [SID1234614752]). The Company is presenting the two posters today at 5:30 p.m. EDT during the Cell Therapies I and Targeted Gene and Cell Therapy I sessions.

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"We have seen impressive clinical results with our first-generation product, afami-cel, in sarcoma, and we set a goal to increase potency to achieve responses in additional indications," said Elliot Norry, Adaptimmune’s Chief Medical Officer. "To that end, we delivered our first next-gen product into the clinic incorporating CD8 and have shown responses across a broad range of solid tumor types in our SURPASS program. We have now presented preclinical data at ASGCT (Free ASGCT Whitepaper) from our second next-gen therapy designed to improve durability and persistence of SPEAR T-cells that supports clinical investigation."

New next-generation SPEAR T-cells show potential for enhanced clinical activity with improved proliferation, survival, and infiltration of immune cells into tumors in preclinical studies

The Company aimed to enhance durability and persistence by engineering a new next-gen SPEAR T-cell targeting MAGE-A4 to secrete IL-7 and CCL19 (ADP-A2M4N7X19) using "Proliferation-Inducing and Migration- Enhancing" (PRIME)1 technology
IL-7 stimulates T-cell proliferation and survival, and CCL19 induces infiltration of immune cells
Naturally occurring T-cells do not express IL-7 or CCL19
Next-generation ADP-A2M4N7X19 SPEAR T-cells were shown to produce IL-7 and CCL19 only in the presence of the MAGE-A4 cancer target
IL-7 production by ADP-A2M4N7X19 SPEAR T-cells enhanced T-cell survival, and CCL19 production induced infiltration of immune cells

Based on these data, Adaptimmune will initiate a Phase 1 clinical trial with ADP-A2M4N7X19 in multiple solid tumor indications
TILs engineered to produce IL-7 may result in a more effective therapy for people with metastatic melanoma with preclinical data demonstrating enhanced TIL survival

TIL therapy has shown some of the most favorable responses in refractory metastatic melanoma2
Adaptimmune applied their lentiviral technology to TILs engineering them to express IL-7 (ADP-TILIL7) with the aim to improve clinical responses

Data indicate that these engineered TILs produce biologically relevant amounts of IL-7; a factor that the TILs cannot produce on their own

IL-7 is known to support T-cell proliferation and survival, which may increase clinical activity and durability of T-cells

Based on these data, a single-center, Phase 1 clinical trial will be initiated at CCIT in Denmark with ADP-TILIL7 to treat patients with metastatic melanoma
The Company will also present a poster entitled "A Novel Flow Cytometry Method for Rapid Assessment of Lentiviral Detection" on May 19th.

On May 16, 2022 Vaccinex, Inc. (Nasdaq: VCNX), a clinical-stage biotechnology company pioneering a differentiated approach to treating cancer and neurodegenerative disease through the inhibition of SEMA4D, reported financial results for the first quarter ended March 31, 2022, and provided a corporate update on key events since the start of 2022 (Press release, Vaccinex, MAY 16, 2022, View Source [SID1234614593]).

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"I am pleased to report that Vaccinex’s clinical programs for oncology and neurodegenerative disease have made substantial progress this year. In oncology, we were gratified to report promising Phase Ib safety results and to observe two complete responses (CRs) in the first three patients enrolled in the open label, Phase 1b/2 KEYNOTE-B84 trial. The trial is evaluating the use of pepinemab in combination with KEYTRUDA (pembrolizumab) as first-line treatment for patients with advanced recurrent or metastatic head and neck cancer. We are hopeful that, with continued positive results, this combination may represent a novel option for patients with head and neck cancer, including those whose tumors express low levels of the PD-L1 biomarker and who have limited treatment choices," said Maurice Zauderer, Ph.D., President and Chief Executive Officer of Vaccinex.

Dr. Zauderer continued, "In neurodegenerative disease, enrollment in the Phase 1/2a SIGNAL-AD trial in mild Alzheimer’s Disease continues to progress, and we plan to soon publish the results of the SIGNAL Huntington’s Disease study that we believe showed promise of slowing or preventing cognitive decline."

Dr. Zauderer continued, "Looking ahead, we expect to complete enrollment in the KEYNOTE-B84 and SIGNAL-AD trials in 2022. Data read outs are planned from the KEYNOTE-B84 during H2:2022 and topline data from the SIGNAL-AD trial are expected in H2:2023. These data will help to guide the regulatory and product development path for pepinemab. We look forward to continue to update the clinical community and investors on our progress."

Pepinemab Clinical Updates and Upcoming Milestones:

Oncology: Head and Neck Cancer

Enrollment is underway in the Phase 1b/2 clinical trial evaluating pepinemab in combination with Merck’s anti-PD-1 immune checkpoint therapy KEYTRUDA (pembrolizumab) in recurrent or metastatic head and neck cancer.

Multiple prior studies1-3 suggest that inhibition of SEMA4D increases immune infiltration and alters the balance of cytotoxic and immunosuppressive cells in the tumor microenvironment. As SEMA4D is highly expressed in head and neck cancer, there is strong rationale for development in this indication.

In January 2022, Vaccinex reported two complete responses in the first three patients enrolled. Vaccinex reported further details of these patient responses (Abstract CT-11) at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (AACR 2022) on Monday, April 11, 2022.

The KEYNOTE-B84 study is planned to enroll up to 65 subjects across 18 U.S. trial sites and will assess whether combination immunotherapy with pepinemab and pembrolizumab can improve responses in this population. Key endpoints of the study will include objective response, progression free survival and overall survival.

Next Data and Trial Completion: Data read-outs are expected in H2:2022. Enrollment is expected to be completed and topline data presented in H1:2023.

ASCO Abstract Publication: An abstract of the Phase 1b segment of the study of pepinemab, an inhibitor of semaphorin 4D, in combination with pembrolizumab as first-line treatment of recurrent or metastatic head and neck cancer (KEYNOTE-B84) will be published with the ASCO (Free ASCO Whitepaper) proceedings on May 26, 2022.

Vaccinex has exclusive global commercial and development rights to pepinemab and is sponsor of the KEYNOTE-B84 study which is being performed in collaboration with Merck Sharp & Dohme Corp, a subsidiary of Merck and Co, Inc. Kenilworth, NJ, USA. KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp. Additional information about the study is available: here.

Other Trials. Pepinemab is also being evaluated in multiple investigator-sponsored trials (ISTs) being conducted by the Winship Cancer Institute of Emory University to evaluate pepinemab in combination with checkpoint inhibitors in "Window of Opportunity" biomarker studies of head and neck cancer and melanoma.

Neurodegenerative Disease:

Alzheimer’s Disease. Enrollment continues in the Phase 1/2a SIGNAL-AD trial of pepinemab in early Alzheimer’s disease which is being funded in part by the Alzheimer’s Drug Discovery Foundation and by a grant from the Alzheimer’s Association under its 2020 Part the Cloud Program. Additional information about this study is available here.

The randomized, double-blind, placebo-controlled, multi-center safety and biomarker study of pepinemab in early AD is planned to enroll 40 subjects across 15 U.S. trial sites.

Next Data and Trial Completion: Enrollment is expected to be completed by year-end 2022 and topline data are expected in H2:2023.

Huntington’s disease. The Phase 2 double-blind, placebo-controlled SIGNAL trial of pepinemab in patients with early manifest Huntington’s disease (HD) has been completed and we believe the program is Phase-3 ready.

While the Phase 2 study did not meet the prespecified primary endpoints, pre-specified exploratory and post-hoc analyses supports the potential cognitive benefit of treatment with pepinemab in HD patients, particularly those with mild cognitive deficits:

Highly significant improvement (p=0.007) in the (Huntington’s Disease Cognitive Assessment Battery (HD-CAB) Composite score
Significant benefit in reducing apathy severity (p=0.017, 1-sided)
Reduced atrophy (p=0.017) in caudate region of striatum
A striking increase in brain metabolic activity as measured by FDG-PET in most brain regions
Next Steps: The company intends to publish the results of the SIGNAL study in mid-2022. In addition, Vaccinex is in ongoing discussions with potential partners on plans to advance pepinemab into a Phase 3 HD trial.

ActivMAb Updates:

As previously announced, we have entered into several collaborations with pharmaceutical and biotechnology companies employing the unique capabilities of our ActivMAb antibody discovery platform to address difficult to drug G-protein Coupled Receptors (GPCRs) and ion channels known to be strongly associated with diseases.

In April, 2022, Vaccinex announced presentation of an abstract at the 18th Annual PEGS Boston Conference & Expo, May 2-3, 2022, related to ActivMAb’s successful expression and selection of antibodies against multi-pass receptors and its potential application as a tool for drug discovery and development projects.

Corporate Update:

In January 2022, the Company sold 8,747,744 shares of the Company’s common stock at a purchase price of $1.11 per share raising aggregate gross proceeds of approximately $9.7 million. In addition, during the first quarter, the company received $3.5 million of net proceeds from the Open Market Sale Agreement by selling 3,115,197 shares of the Company’s common stock at a weighted average price of $1.16 per share.

Financial Results for the Three Months Ended March 31, 2022:
Cash and Cash Equivalents and Marketable Securities. Cash and cash equivalents and marketable securities on March 31, 2022 were $16.8 million, as compared to $8.6 million as of December 31, 2021.

Research and Development Expenses. Research and development expenses for the quarter ended March 31, 2022 were $3.0 million as compared to $5.5 million for the comparable period in 2021.

Research and Development expenses are lower in 2022 compared to 2021 primarily attributed to reduced clinical trial costs as a result of the completion of the CLASSICAL-Lung and SIGNAL studies, partially offset by setup expenses for the KEYNOTE B84 and SIGNAL-AD studies as well as a large production run of pepinemab completed in Q1:21.

General and Administrative Expenses. General and administrative expenses for the quarter ended March 31, 2022 were $1.6 million as compared to $1.6 million for the comparable period in 2021.

Essentially flat level of general and administrative expenses reflects careful cost control measures in light of inflationary pressures.

Comprehensive loss/Net loss per share. The Comprehensive Loss and Net loss per share for the quarter ended March 31, 2022 was $4.6 million and $0.12, respectively, compared to $6.6 million and $0.26 for the comparable period in 2021.

Full financial tables are included below. For further details on Vaccinex’s financials, refer to its Form 10-Q filed May 16, 2022, with the Securities and Exchange Commission

REFERENCES:

Shafique MR, Fisher TL, Evans EE, Leonard JEE, Pastore DRE, Mallow CL, Smith E, Mishra V, Schroder A, Chin KA, Beck JT, Baumgart MA, Govindan R, Gabrial NY, Spira AI, Seetharamu N, Lou Y, Mansfield AS, Sanborn RE, Goldman JW, Zauderer M. A Phase Ib/2 Study of Pepinemab in Combination with Avelumab in Advanced Non–Small Cell Lung Cancer. Clin Cancer Res 2021, doi: 10.1158/1078-0432.CCR-20-4792
Clavijo PE, Friedman J, Robbins Y, Moore EC, Smith ES, Zauderer M, Evans EE, Allen CT. Semaphorin4D inhibition improves response to immune checkpoint blockade via attenuation of MDSC recruitment and function. Cancer Immunol Res. 2019 Feb;7(2):282-291
Evans EE, Jonason AS Jr, Bussler H, Torno S, Veeraraghavan J, Reilly C, Doherty MA, Seils J, Winter LA, Mallow C, Kirk R, Howell A, Giralico S, Scrivens M, Klimatcheva K, Fisher TL, Bowers WJ, Paris M, Smith ES, Zauderer M. Antibody blockade of semaphorin 4D promotes immune infiltration into tumor and enhances response to other immunomodulatory therapies. Cancer Immunol Res. 2015 Jun;3(6): 689-701. View Source
About Pepinemab
Pepinemab is a humanized IgG4 monoclonal antibody that inhibits SEMA4D, which regulates the actin cytoskeleton of cells that plays an important role in tumor immunity and cell interactions in the brain. Preclinical and clinical data show that pepinemab promotes infiltration/activation of dendritic cells and CD8+ T-cells and reverses immunosuppression within the tumor microenvironment. Pepinemab is being evaluated in several studies in oncology and neurodegenerative disease.

About ActivMAb
Vaccinex has developed a proprietary mammalian cell-based antibody discovery platform with unique multi-pass membrane target capabilities. The ActivMAb technology now has four main applications: complex membrane antigen presentation, antibody or antigen discovery, and protein optimization. Vaccinex has entered into an antibody license with Surface Oncology (Cambridge, MA) and into Material Transfer Agreements for drug discovery or process development with major pharmas utilizing this technology. Vaccinex seeks partnering opportunities for co-development or licensing of existing antibodies in our pipeline, discovery of new antibodies and/or applications for this powerful technology.