On March 14, 2024 AC Immune SA (NASDAQ: ACIU), a clinical-stage biopharmaceutical company pioneering the development of precision medicine approaches for the diagnosis, treatment, and prevention of neurodegenerative diseases, reported results for the year ended December 31, 2023, and provided a corporate update (Press release, AC Immune, MAR 14, 2024, View Source [SID1234641149]).

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Dr. Andrea Pfeifer, CEO of AC Immune SA, commented: "We made significant progress in 2023 advancing our three innovative active immunotherapy programs in Phase 2 clinical trials in Alzheimer’s and Parkinson’s diseases. This sets the stage for a number of important milestones in 2024, which have the potential to further enhance our understanding of how best to prevent neurodegeneration and to generate significant value for AC Immune. In the second quarter and second half of 2024, we will be reporting Phase 2 ACI-24.060 data on amyloid plaque reduction after 6- and 12-months treatment, respectively. Amyloid plaque is a clinically validated biomarker of efficacy, making these data announcements potentially de-risking and providing an opportunity to accelerate ACI-24.060 into a registrational program.

"We are also delighted that ACI-35.030 (JNJ-64042056), our anti-phospho-Tau active immunotherapy, has now entered the Phase 2b trial, conducted by our partner in pre-symptomatic AD patients. In addition, our ACI-7104.056 anti-alpha-synuclein active immunotherapy is advancing through Phase 2 testing for Parkinson’s disease (PD) with initial safety and immunogenicity data expected in the second half of 2024.

"AC Immune’s primary focus remains on these three active immunotherapy programs, each of which has the potential to transform how neurodegenerative diseases are treated and ultimately, to enable precision prevention of these diseases. Thanks to our strengthened leadership team and reinforced balance sheet, we are well-positioned to deliver de-risking clinical milestones, working towards our mission to shift the paradigm from disease treatment to disease prevention."

2023 and Subsequent Highlights

Active Immunotherapy Programs

ACI-24.060 anti-Abeta active immunotherapy

· Received Fast Track Designation from the U.S. Food and Drug Administration for the treatment of AD

· The enrolment in the ABATE Phase 2 AD trial continues with cohort 3 now being expanded. Following data safety monitoring board (DSMB) review, no safety concerns have been raised to date, consistent with the previously observed safety profile.

· Initial interim ABATE safety and immunogenicity data from the first, low dose AD cohort were promising, with clear evidence of anti-Abeta antibody responses against toxic Abeta species observed in the blinded data.

· The first participant with Down syndrome (DS) was dosed in the Phase 2 ABATE trial.

· Six-month Abeta positron emission tomography (PET) imaging results are expected in Q2 2024, and 12-month Abeta-PET data are expected in H2 2024.

ACI-35.030 (JNJ-64042056) anti-phospho-Tau (anti-pTau) active immunotherapy

· Phase 2b ReTain clinical trial in participants with preclinical AD preparations are ongoing to initiate the study by H1 2024 by Janssen Pharmaceuticals, Inc., a Johnson & Johnson company (Janssen).

· ReTain will evaluate the effect of ACI-35.030 on cognition and Tau pathology in approximately 500 participants with preclinical AD. These will be randomized in a 1:1 ratio to a single dose level of ACI-35.030 or placebo, administered as intramuscular injections for a maximum of 4 years.

· Under the terms of the licensing agreement, AC Immune received a milestone payment of CHF 15 million on February 1, 2024 and expects to receive another milestone payment of CHF 25 million related to achieving an undisclosed enrolment target in 2025.

ACI-7104.056 anti-a-syn active immunotherapy

· Completed enrolment of cohort 1 in the VacSYn Phase 2 trial in Parkinson’s disease (PD), with 16 patients randomized. Enrolment and randomization of cohort 2 is ongoing as planned.

· No safety concerns have been reported to date with no reports of moderate or severe adverse events. Safety and immunogenicity updates from the trial are expected in H2 2024.

Diagnostic Programs

· A peer-reviewed paper published in Nature Communications (Smith et al., Nat. Comm., 2023) showed that AC Immune’s wholly-owned a-syn-PET tracer ACI-12589 can detect a-syn pathology in multiple system atrophy (MSA) and differentiate MSA from other a-synucleinopathies.

· The TDP-43-PET tracer program has progressed as planned and a clinical candidate has been selected. Further IND-enabling studies will be completed over the coming months to permit the initiation of a Phase 1 clinical trial in H2 2024.

· In the pivotal Phase 3 ADvance trial evaluating the Morphomer derived Tau-PET tracer, PI-2620 in AD, the first participant was imaged and the study is progressing well. PI-2620 was discovered and developed using the Morphomer platform as part of a research collaboration between AC Immune and Life Molecular Imaging.

Corporate Updates

· Completed USD 50 million equity financing in December 2023, extending cash runway into Q1 2026. (This assumes the second ACI-35-related milestone payment of CHF 25 million is received in 2025)

· New grants that collectively provide more than USD 500,000 in additional non-dilutive capital to support the advancement of diagnostic programs targeting TDP-43 (TAR DNA-binding protein 43) were awarded to AC Immune by The Michael J. Fox Foundation for Parkinson’s Research (MJFF) and the Target ALS Foundation.

· Strengthened leadership team with appointments of Dr. Nuno Mendonça as Chief Medical Officer, Dr. Madiha Derouazi as Chief Scientific Officer, and Mr. Christopher Roberts as Chief Financial Officer.

Thought Leadership and Collaborations

· Initiated a research collaboration with Prof. Michael Heneka, director of the Luxembourg Centre for Systems Biomedicine, University of Luxembourg, to evaluate the therapeutic potential of AC Immune’s SupraAntigen- and Morphomer-derived inhibitors of the NLRP3-ASC inflammasome pathway in preclinical disease models.

· Hosted webinar on PET imaging in AD featuring key opinion leader (KOL) Victor Villemagne, M.D. (University of Pittsburg).

· Hosted KOL webinar on early diagnosis and prevention of AD featuring presentations by Kaj Blennow, MD, PhD, of University of Gothenburg and Sahlgrenska University Hospital, and Giovanni Frisoni, MD, of University of Geneva and the Memory Clinic at Geneva University Hospital.

Anticipated 2024 Milestones

ACI-24.060
anti-Abeta active immunotherapy
· 6-month and 12-month Abeta-PET data in AD expected in Q2 2024 and H2 2024, respectively

· Initial safety and immunogenicity data in DS cohort expected in H2 2024

ACI-7104.056
anti-a-syn active immunotherapy · Interim safety and immunogenicity update from the Phase 2 VacSYn study in Parkinson’s disease expected in H2 2024
ACI-35.030
anti-pTau active immunotherapy · First-patient in ReTain Phase 2b clinical trial expected in H1 2024
Anti-TDP-43 antibody · Completion of regulatory tox studies expected in H1 2024
TDP-43-PET tracer · Phase 1 initiation expected in H2 2024
ACI-15916

a-syn-PET tracer

· IND-enabling studies in PD expected to be completed in H2 2024

Analysis of Financial Statements for the Year Ended December 31, 2023

· Cash Position: The Company had a total cash balance of CHF 103.1 million as of December 31, 2023, compared to a total cash balance of CHF 122.6 million as of December 31, 2022. On February 1, 2024, the Company received the milestone payment of CHF 14.8 million from Janssen for the commencement of ReTain, the ACI-35.030 Phase 2b clinical study. The Company’s cash balance provides sufficient capital resources to progress into at least Q1 2026, assuming potential milestone payment of CHF 24.6 million related to achieving an undisclosed enrolment target for our ACI-35.030 and no other milestones.

· Contract Revenues: The Company recorded CHF 14.8 million in contract revenues for the year end December 31, 2023 compared with CHF 3.9 million in contract revenues in the prior year. For the year ended December 31, 2023, our contract revenues of CHF 14.8 million were related to the commencement of the first Phase 2b clinical study of ACI-35.030 per our agreement with Janssen.

· R&D Expenditures: R&D expenses decreased by CHF 5.7 million for the year ended December 31, 2023 to CHF 54.6 million, predominantly due to:

o Discovery and preclinical expenses (- CHF 5.8 million): The Company decreased expenditures across a variety of its discovery and preclinical programs.
o Clinical expenses (- CHF 2.0 million): The Company had a net decrease in clinical expenditures largely due the completion of the Phase 1b/2a and the advancement into Phase 2b for our ACI-35.030 active immunotherapy. We increased expenditures for the continued clinical development of our Phase 1b/2 ABATE study for ACI-24.060.
o Salary- and benefit-related costs (+ CHF 2.2 million): While the staffing position remained stable in 2023, personnel expenses increased due to the annualization of 2022 hires.

· G&A Expenditures: G&A expenses decreased by CHF 0.5 million for the year ended December 31, 2023 to CHF 15.3 million. This decrease is related to a decrease in operating expenses across various cost centers. This is partially offset by an increase in salaries and related costs.

· Other Operating Income: The Company recorded CHF 1.4 million in grant income for R&D activities performed under our grants for the year ended December 31, 2023.

· IFRS Loss for the Period: The Company reported a net loss after taxes of CHF 54.2 million for the year ended December 31, 2023, compared with a net loss of CHF 70.8 million for the prior period.

On February 10, 2021, Molecular Templates, Inc. (the "Company"), reported to have entered into a Collaboration Agreement (the "Collaboration Agreement") with Bristol Myers Squibb Company ("BMS"), pursuant to which the parties agreed to enter into a strategic research collaboration to leverage the Company’s engineered toxin body ("ETB") technology platform to discover and develop novel products containing ETBs directed to multiple targets (Filing, 8-K, Molecular Templates, MAR 13, 2024, View Source [SID1234641203]). Pursuant to the terms of the Collaboration Agreement, the Company granted BMS a series of exclusive options to obtain one or more exclusive licenses under the Company’s intellectual property to exploit products containing ETBs directed against certain targets designated by BMS.

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Following a corporate portfolio prioritization process, BMS notified the Company on March 13, 2024 that it does not intend to continue the research collaboration it entered into with the Company pursuant to the Collaboration Agreement and would be terminating the Collaboration Agreement in its entirety. The termination will be effective on June 13, 2024, or 90 days following the Company’s receipt of BMS’s written notice of termination. The Company will reduce costs associated with the Collaboration Agreement and focus its resources exclusively on its wholly-owned clinical-stage programs.

On March 13, 2024 Affini-T Therapeutics, Inc., a precision immunotherapy company unlocking the power of T cells against oncogenic driver mutations, reported that preclinical data from its oncogenic driver programs targeting HLA-A*11:01 KRAS G12D and HLA-A*02:01 p53 R175H will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 held in San Diego, CA (Press release, Affini-T Therapeutics, MAR 13, 2024, View Source [SID1234641131]). In addition, two trial-in-progress posters for Affini-T’s Phase 1 clinical-stage programs targeting KRAS G12V, the company-sponsored AFNT-211 study and the Fred Hutchinson Cancer Center investigator-initiated AFNT-111 study, will be presented at the same conference.

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Poster presentation details are as follows:

Title: Non-viral engineered T cell therapy specific for the hotspot mutation p53 R175H that integrates signal 1 (TCR), signal 2 (co-stimulation) and signal 3 (cytokine) and co-opts FasL-dependent apoptosis to achieve a coordinated antitumor CD4/8 T cell response
Session: Adoptive Cell Therapies 1: Tumor Antigen-Specific T-cells and TCR-T
Abstract Number: 7242
Presenting Author: Gary Shapiro, Ph.D., VP Biology Discovery, Affini-T Therapeutics
Date/Time: Sunday, April 7, 2024, 1:30 PM – 5:00 PM

Title: AFNT-212: A TRAC-knocked-in KRAS G12D-specific TCR-T cell product enhanced with CD8αβ and a chimeric cytokine receptor for treatment of solid cancers
Session: Adoptive Cell Therapies 1: Tumor Antigen-Specific T-cells and TCR-T
Abstract Number: 5973
Presenting Author: Loïc Vincent, Ph.D., Chief Scientific Officer, Affini-T Therapeutics
Date/Time: Sunday, April 7, 2024, 1:30 PM – 5:00 PM

Title: Identifying novel patient-derived T cell receptors targeting TP53 public neoantigens
Session: Adoptive Cell Therapies 1: Tumor Antigen-Specific T-cells and TCR-T
Abstract Number: 441
Presenting Author: Michael V. Gormally, M.D., Ph.D., Fellow, Memorial Sloan Kettering Cancer Center
Date/Time: Sunday, April 7, 2024, 1:30 PM – 5:00 PM

Title: AFNT-211: A phase 1 study of autologous CD4+ and CD8+ T cells engineered to express a high avidity HLA-A*11:01-restricted, KRAS G12V-specific, transgenic TCR; CD8α/β coreceptor; and a FAS41BB switch receptor in patients with advanced/metastatic solid tumors
Session: Phase I Clinical Trials in Progress 1
Abstract Number: CT076
Presenting Author: Dirk Nagorsen, M.D., Chief Medical Officer, Affini-T Therapeutics
Date/Time: Monday, April 8, 2024, 9:00 AM – 12:30 PM

Title: Phase I study of autologous CD8+ and CD4+ transgenic T cells expressing high-affinity KRAS G12V mutation-specific T cell receptors (FH-A11KRASG12V-TCR) in patients with metastatic pancreatic, colorectal, and non-small cell lung cancers with KRAS G12V mutations
Session: Phase I Clinical Trials in Progress 1
Abstract Number: CT082
Presenting Author: Aude G. Chapuis, M.D., Fred Hutchinson Cancer Center
Date/Time: Monday, April 8, 2024, 9:00 AM – 12:30 PM

About Affini-T Therapeutics

On March 13, 2024 Xcovery Holdings, Inc., an oncology focused pharmaceutical company, reported that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for ensartinib, an Anaplastic Lymphoma Kinase (ALK) inhibitor for the treatment of adult patients with metastatic ALK-positive non-small cell lung cancer (NSCLC) (Press release, Xcovery, MAR 13, 2024, View Source [SID1234641130]). The filing is based on the results of the eXalt3, a randomized global phase III study designed to evaluate the efficacy and safety of ensartinib vs crizotinib in the first-line treatment of ALK-positive NSCLC. The FDA granted the application Standard Review and assigned a Prescription Drug User Fee Act (PDUFA) goal date of December 28, 2024.

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"The FDA’s acceptance of this NDA represents a key milestone for Xcovery in its mission to bring ensartinib as a novel and distinct first-line therapeutic option to ALK-positive NSCLC patients"

"The FDA’s acceptance of this NDA represents a key milestone for Xcovery in its mission to bring ensartinib as a novel and distinct first-line therapeutic option to ALK-positive NSCLC patients," said Giovanni Selvaggi, M.D., Chief Medical Officer of Xcovery. "We will continue to work closely with the agency during the review period. This achievement is a testament to our patient-centric vision and has been made possible by the dedication and skills of the entire Xcovery team and stakeholders, with the constant support of the patients, their families and investigators in our clinical trials globally."

Ensartinib is a next generation ALK inhibitor jointly developed by Xcovery and Betta Pharmaceuticals. In the clinical trials, the drug has demonstrated robust and durable responses in ALK-positive NSCLC patients (both systemically and in the brain), with an extensively studied and well manageable safety profile. The results of the eXalt3 were originally published in JAMA Oncology in September 2021.

On March 13, 2024 Zephyr AI, Inc. ("Zephyr AI"), a healthcare technology company committed to developing fast and explainable Artificial Intelligence (AI) solutions to democratize precision medicine, reported it has successfully closed a $111 million Series A funding round with participation from Revolution Growth, Eli Lilly & Company, Jeff Skoll, and EPIQ Capital Group, among others (Press release, Zephyr AI, MAR 13, 2024, View Source [SID1234641129]). The company is developing improved data federation tools along with various machine learning algorithms in the areas of oncology and cardiometabolic disease.

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"The expansion of our diverse multimodal data resources will accelerate the advancement of Zephyr AI’s algorithms, paving the way for us to transform the landscape of precision medicine and improve outcomes for our partners and patients."

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"The US has the highest rate of avoidable cancer and cardiometabolic-related deaths among any high-income country. We must do better," said Grant Verstandig, Zephyr AI’s Co-Founder and Executive Chairman. "At Zephyr AI, we are harnessing the power of AI to extract novel insights to better define patient stratification and response predictions as well as improve federation of real-world data. With our world-class team, and the support of this investor group, we are deploying one of the largest clinicogenomic datasets that has unprecedented breadth across disease states and data partners. Collectively, we are now well positioned to support our mission of democratizing precision medicine, enhancing both the speed and success of clinical trials."

According to Dr. Justin Stebbing, Chairman of Zephyr AI’s Scientific and Medical Advisory Board, Editor of Oncogene (published under the Nature portfolio), and Professor of Biomedical Sciences at ARU, Cambridge, the company’s technology stands out along two crucial dimensions. "First, it has empirically demonstrated the ability to navigate the intricacies of real-world patient data, historically a challenge in the field. Second, leveraging recent breakthroughs in representation learning, the technology elucidates the biological context underlying its predictions. This contextual understanding is pivotal in drug development decision-making, revealing patient selection insights unpredictable using today’s tools to maximize the value of both approved medicines and drugs in development."

The new funds will enable Zephyr AI to further enhance its analytical speed and fortify its extensive collection of training and validation data sets. Moreover, the funds will support the expansion of the company’s scientific and commercial teams to expedite the delivery of its rapidly growing pipeline of insights to the market.

"The expansion of our diverse multimodal data resources will accelerate the advancement of Zephyr AI’s algorithms, paving the way for us to transform the landscape of precision medicine and improve outcomes for our partners and patients," said Jeff Sherman, Co-Founder, Interim CEO, and Chief Technology Officer of Zephyr AI.

Zephyr AI has had two abstracts accepted for publication at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting to be held in San Diego on April 5-10, 2024.

1)

Abstract # 3519/11: Reconstructing a latent representation of gene expression from genomic alterations to improve clinical utility of real-world clinicogenomics data presented by Maayan Baron et al., Monday April 8th, 1.30 – 5.00pm

2)

Abstract #7373/1: Generative Bayesian networks for augmentation of molecular data from commercial genetic panels presented by Dillon Tracy et al., Wednesday April 10th 9.00 – 12.30pm

"We are excited to be part of this growing ecosystem of AI-enabled drug development and welcome the opportunity to attend AACR (Free AACR Whitepaper) where we will engage with the scientific community and present some of our emerging scientific insights from our platform," Sherman said.

Cooley LLP served as legal counsel for Zephyr AI.