On March 14, 2024 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer and autoimmune disease, reported a corporate update and provided financial results for the quarter and year ended December 31, 2023 (Press release, Allogene, MAR 14, 2024, View Source [SID1234641153]).

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"We are more enthusiastic than ever about the potential for allogeneic CAR T to transform the field," said David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder of Allogene. "From our innovative ALPHA3 trial which is designed to embed cema-cel as part of a curative first-line regimen for patients with large B cell lymphoma, to specifically creating a CAR T that can meet the unique needs of patients with autoimmune disease and reduce reliance on lymphodepletion, our development approach focuses on the distinctive attributes of an off-the-shelf alternative and creates an advantage for our AlloCAR T programs."

Core Program Updates

Cema-Cel: Pivotal ALPHA3 1L Consolidation Trial in Large B Cell Lymphoma (LBCL)
The Company continues to focus on the development of its investigational product cemacabtagene ansegedleucel, or cema-cel (previously known as ALLO-501A) as part of the first line (1L) treatment plan for LBCL patients who are likely to relapse following 1L chemoimmunotherapy.

This innovative trial takes advantage of the unique attributes of cema-cel, the only allogeneic cell therapy product with Phase 1 data comparable to that of an autologous therapy. With off-the-shelf availability and convenience, cema-cel will be administered as a one-time infusion immediately upon detection of minimal residual disease (MRD) at the completion of six cycles of R-CHOP or equivalent 1L chemoimmunotherapy. The potential outcome of this consolidation treatment could improve the cure rate and uniquely position cema-cel to become the standard "7th cycle" of frontline treatment available to all eligible patients with MRD.

The design of the ALPHA3 1L consolidation trial builds upon the results demonstrated in the cema-cel Phase 1 ALPHA2 trial and will leverage an investigational, cutting-edge diagnostic test for MRD developed by Foresight Diagnostics. ALPHA3 will randomize approximately 230 patients who are in clinical remission but remain MRD positive at the end of standard 1L chemoimmunotherapy to either consolidation with cema-cel or the current standard of care, observation, which means to "watch and wait" for the disease to relapse. The primary endpoint of the ALPHA3 trial is event free survival (EFS). The trial will initially test two lymphodepletion regimens (one with standard fludarabine and cyclophosphamide plus ALLO-647 and one without ALLO-647). One lymphodepletion arm will be discontinued following a planned interim analysis in mid-2025 designed to select the most appropriate regimen for this patient population.

Start-up activities for the ALPHA3 trial are underway and the trial is expected to begin in mid-2024. The ALPHA3 trial will be conducted in a wide array of cancer treatment centers, including community cancer centers where most earlier line patients seek care.

Cema-Cel: Phase 1 ALPHA2 Trial in Chronic Lymphocytic Leukemia (CLL)
In the first quarter, the Company began enrollment in the ALPHA2 trial of the investigational product cema-cel in patients with relapsed/refractory (r/r) CLL. While recent autologous CD19 CAR T data has been a positive step for patients with relapsed/refractory (r/r) CLL, T cell dysfunction and high circulating leukemia burden often found in patients with CLL, make the isolation of functional T cells for autologous CAR T manufacturing difficult. As a result, this trial has been driven by investigator enthusiasm for an allogeneic CAR T to potentially boost the curative power of CAR T.

Initial data readout from Phase 1 ALPHA2 CLL cohort (n=12) is projected by year-end 2024.

ALLO-329: CD19 Dagger in Autoimmune Disease (AID)
The Company has applied its deep understanding of CAR T research and development to design next-generation allogeneic CAR T investigational products that the Company believes can sustain the scale of the AID market while also meeting the unique requirements for these patients where they seek care.

ALLO-329, the Company’s first AlloCAR T investigational product for AID, incorporates the Dagger technology which is intended to reduce or eliminate the need for lymphodepletion while targeting CD19+ B-cells and CD70+ activated T-cells, both of which play a role in AID.

As part of its overarching AID 2.0 platform, the Company also announced a non-exclusive, global gene editing licensing agreement with Arbor Biotechnologies, Inc. for use of their proprietary CRISPR-based gene-editing technology.

ALLO-329 is expected to enter Phase 1 clinical trials in early 2025.

ALLO-316: TRAVERSE Trial in Renal Cell Carcinoma (RCC)
Building upon the field’s understanding of how certain drugs can act as a "safety key" to mitigate treatment-associated adverse events without compromising CAR T function or efficacy, the Company has developed and implemented a diagnostic and treatment algorithm in its solid tumor trial that may mitigate the treatment-associated hyperinflammatory response without compromising the CAR T function needed to eradicate solid tumors with ALLO-316 in renal cell carcinoma (RCC).

Details on this potentially cornerstone discovery in the Phase 1 TRAVERSE trial is planned for a publication in Q2 2024. A more comprehensive data update from the ongoing trial with the updated protocol is planned for later in 2024.

Financial Updates
As noted in the February 16, 2024 press release, the Company has now issued restated financials for the years ended December 31, 2020, 2021 and 2022 and interim quarters during 2022 and 2023 due to non-cash accounting adjustments associated with the December 2020 formation of the Allogene Overland Biopharm joint venture in Asia. These restated financial statements have no impact on the Company’s cash, cash equivalents and marketable investments, cash runway or business operations.

2023 Fourth Quarter and Year-End Financial Results

Research and development expenses were $54.7 million for the fourth quarter of 2023, which includes $7.0 million of non-cash stock-based compensation expense. For the full year of 2023, research and development expenses were $242.9 million, which includes $31.9 million of non-cash stock-based compensation expense.
General and administrative expenses were $17.2 million for the fourth quarter of 2023, which includes $8.2 million of non-cash stock-based compensation expense. For the full year of 2023, general and administrative expenses were $71.7 million, which includes $34.0 million of non-cash stock-based compensation expense.
Net loss for the fourth quarter of 2023 was $85.8 million, or $0.51 per share, including non-cash stock-based compensation expense of $15.2 million and $13.2 million in non-cash impairment of long-lived asset expense. For the full year of 2023, net loss was $327.3 million, or $2.09 per share, including non-cash stock-based compensation expense of $66.0 million and $13.2 million in non-cash impairment of long-lived asset expense.
The Company had $448.7 million in cash, cash equivalents, and investments as of December 31, 2023.
2024 Financial Guidance
The Company expects a decrease in cash, cash equivalents, and investments of approximately $190 million in 2024. Based on current assumptions, the Company continues to expect its cash runway to fund operations into 2026. GAAP Operating Expenses are expected to be approximately $280 million, including estimated non-cash stock-based compensation expense of approximately $60 million. These estimates exclude any impact from potential business development activities.

Conference Call and Webcast Details
Allogene will host a live conference call and webcast today at 2:00 p.m. Pacific Time / 5:00 p.m. Eastern Time to discuss financial results and provide a business update. If you would like the option to ask a question on the conference call, please use this link to register. Upon registering for the conference call, you will receive a personal PIN to access the call, which will identify you as the participant and allow you the option to ask a question. The listen-only webcast will be made available on the Company’s website at www.allogene.com under the Investors tab in the News and Events section. Following the live audio webcast, a replay will be available on the Company’s website for approximately 30 days.

On March 14, 2024 Allakos Inc. (the "Company") (Nasdaq: ALLK), a biotechnology company developing antibodies for the treatment of allergic, inflammatory and proliferative diseases, reported a business update and provided financial results for the fourth quarter and full year ended December 31, 2023 (Press release, Allakos, MAR 14, 2024, View Source [SID1234641152]).

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Recent Allakos Events

Completed dosing in the single ascending dose (SAD) cohorts and continued dosing in the multiple ascending dose (MAD) cohorts of the randomized, double-blind, placebo-controlled Phase 1 trial of Intravenous (IV) AK006 in healthy volunteers.
Initiated the randomized, double-blind, placebo-controlled subcutaneous (SC) AK006 cohort in healthy volunteers.
Published preclinical research in Allergy showing that AK006 controls mast cell function through interaction with multiple activating receptors and key signaling pathways.
Presented preclinical data at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting 2024 highlighting AK006’s mechanism of action and ability to reduce MRGPRX2-induced skin inflammation.
Reported topline data from the Phase 2 study of SC lirentelimab in patients with atopic dermatitis and Phase 2b study of SC lirentelimab in patients with chronic spontaneous urticaria.
Halted lirentelimab-related development activities and announced a restructuring plan to reduce costs and focus on AK006 clinical development. As a result of the restructuring, Allakos expects its cash runway to extend into mid-2026.
Upcoming Allakos Anticipated Milestones

Report safety, pharmacokinetics (PK), and pharmacodynamic (PD) results from the Phase 1 trial of IV AK006 in healthy volunteers, including data to confirm Siglec-6 receptor occupancy in skin biopsy samples in Q2 2024.
Initiate the randomized, double-blind, placebo-controlled Phase 1 trial of IV AK006 in patients with chronic spontaneous urticaria in Q2 2024.
Report safety, PK, and PD results from the Phase 1 trial of SC AK006 in healthy volunteers, including data to confirm Siglec-6 receptor occupancy in skin biopsy samples in Q3 2024.
Report topline data from the Phase 1 trial of IV AK006 in patients with CSU at year end 2024
Cash Guidance

The Company expects that the restructuring activities will extend the cash runway into mid-2026.

The Company ended the fourth quarter of 2023 with approximately $170.8 million in cash, cash equivalents and investments. The Company’s outlook for 2024 cash, cash equivalents and investments is as follows:

Cash, cash equivalents and investments at year end 2023 $171 million
Estimated 2024 net cash used in operating activities (GAAP) ($85 to $90 million)
Estimated cash, cash equivalents and investments at year end 2024 $81 to $86 million

Components of estimated 2024 net cash used in operating activities for the year ended December 31, 2024 are as follows:

Estimated net cash used in operating activities (GAAP) $85 to $90 million
Less: estimated lirentelimab closeout, severance and other costs 1 ($30 million)
Estimated adjusted net cash used in operating activities (non-GAAP) 2 $55 to $60 million

1 The Company anticipates that the significant majority of the restructuring expenditures, including approximately $4 million of severance, will be paid in the first half of 2024.

2 For additional information on the Company’s use of non-GAAP financial information, please see the section titled "Non-GAAP Financial Measure" below.

Fourth Quarter 2023 Financial Results

Research and development expenses were $53.8 million in the fourth quarter of 2023 compared to $35.4 million in the fourth quarter of 2022, an increase of $18.4 million. This quarter over quarter increase is attributed to $15.0 million of increased manufacturing costs and $3.4 million of increased other research and development expenses related primarily to our clinical studies.

General and administrative expenses were $11.2 million for the fourth quarter of 2023 compared to $10.8 million for the fourth quarter of 2022, an increase of $0.4 million. The quarter over quarter change included $0.3 million of increase stock-based compensation expenses and $0.1 million increase in other general and administrative expenses.

Allakos reported a net loss of $62.6 million in the fourth quarter of 2023 compared to $43.0 million in the fourth quarter of 2022. The fourth quarter of 2023 included noncash expenses for stock-based compensation of $10.2 million, compared to $9.3 million in the same period in 2023, and depreciation expense of $1.5 million in each of the fourth quarters of 2023 and 2022. Net loss per basic and diluted share was $0.71 for the fourth quarter of 2023 compared to $0.50 in the fourth quarter of 2022.

Allakos ended the fourth quarter of 2023 with $170.8 million in cash, cash equivalents and investments resulting in a net decrease in cash, cash equivalents and investments of $23.1 million during the fourth quarter of 2023.

On March 14, 2024 Akebia Therapeutics, Inc. (Nasdaq: AKBA), a biopharmaceutical company with the purpose to better the lives of people impacted by kidney disease, reported financial results for the fourth quarter and full year ended December 31, 2023 and recent business highlights. Akebia is preparing for a potential launch of vadadustat, which is currently under review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) date of March 27, 2024 (Press release, Akebia, MAR 14, 2024, View Source [SID1234641151]).

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"We are eagerly awaiting the PDUFA date for vadadustat, now within weeks, and we believe the progress we have made over the past 12 months has positioned our team to successfully launch vadadustat in the U.S., if approved," said John P. Butler, Chief Executive Officer of Akebia. "A U.S. approval for vadadustat will be transformational for Akebia and a significant step toward our goal of bettering the lives of people impacted by kidney disease. Our team remains dedicated to delivering an innovative oral therapeutic treatment for anemia due to chronic kidney disease for patients on dialysis."

Fourth Quarter 2023 and Recent Business Highlights:

•Appointed Nicholas Grund as Chief Commercial Officer, who brings years of expertise in customer-facing roles to Akebia. Mr. Grund’s operational, commercial and strategic leadership experience across renal and specialty markets will be critical as Akebia prepares for the vadadustat launch in the U.S., if approved.

•Introduced new pipeline programs in acute care settings, potentially for acute kidney injury or acute respiratory distress syndrome (AKB-9090) and retinopathy of prematurity in neonates (AKB-10108).

•Closed a new debt facility with BlackRock that provides access to up to $55.0 million in borrowing capacity and used the proceeds from the first tranche of $37.0 million to pay down principal outstanding under the then loan agreement with Pharmakon Advisors, LP. The BlackRock debt facility, which closed on January 29, 2024, also extends the interest-only period in the event of vadadustat approval in the U.S. on or prior to June 30, 2024 without requiring any principal repayment until December 31, 2026.

•Concluded its offering of common stock under its "at-the-market" (ATM) sales agreement. Akebia raised approximately $26.0 million in gross proceeds.

Akebia reported fourth quarter 2023 Auryxia (ferric citrate) net product revenues of $53.2 million and full year 2023 revenues of $170.3 million, within Akebia’s 2023 Auryxia net product revenue guidance of $170.0 – $175.0 million.

"We are approaching a potential U.S. launch of vadadustat from an extremely strong financial position. We expect Auryxia net product revenue growth in 2024, with a quarterly revenue cadence that is similar to 2023, we executed a term loan with BlackRock and implemented other financial strategies that together we believe will support our business operations for at least two years if vadadustat is approved. As we move forward, we will continue to carefully manage expenses, while investing appropriately for a successful potential launch of vadadustat," Mr. Butler added.

Financial Results

•Revenues: Total revenues were $56.2 million for the fourth quarter of 2023 compared to $55.8 million for the fourth quarter of 2022, and $194.6 million for the full-year 2023 compared to $292.5 million for the full-year 2022.

◦Net product revenues were $53.2 million for the fourth quarter of 2023 compared to $50.3 million for the fourth quarter of 2022, and $170.3 million for the full-year 2023 compared to $176.9 million for the full-year 2022.

◦License, collaboration and other revenues were $3.0 million for the fourth quarter of 2023 compared to $5.5 million for the fourth quarter of 2022, and $24.3 million for the full-year 2023 compared to $115.5 million for the full-year 2022.

•COGS: Cost of goods sold was $18.7 million for the fourth quarter of 2023 compared to a benefit of $3.4 million for the fourth quarter of 2022, and $74.1 million for the full-year 2023 compared to $85.6 million for the full-year 2022. Akebia continues to record a non-cash intangible amortization charge of $9.0 million per quarter through the fourth quarter of 2024.

•R&D Expenses: Research and development expenses were $9.9 million for the fourth quarter of 2023 compared to $32.1 million for the fourth quarter of 2022, and $63.1 million for the full-year 2023 compared to $130.0 million for the full-year 2022.

•SG&A Expenses: Selling, general and administrative expenses were $25.4 million for the fourth quarter of 2023 compared to $29.9 million for the fourth quarter of 2022, and $100.2 million for the full-year 2023 compared to $138.6 million for the full-year 2022.

•Net Income / Loss: Net income was $0.6 million for the fourth quarter of 2023 compared to a net loss of $6.1 million for the fourth quarter of 2022, and $51.9 million for the full-year 2023 compared to $94.2 million for the full-year 2022.

•Cash Position: Cash and cash equivalents as of December 31, 2023, were approximately $42.9 million. Akebia believes its existing cash resources and the cash it expects to generate from product, royalty, supply and license revenues as well as the borrowings and potential future borrowings that are available under the BlackRock debt facility and the working capital liability are sufficient to fund our current operating plan for at least twenty-four months if vadadustat is approved.

On March 12, 2024 Agenus Inc. ("Agenus") (Nasdaq: AGEN), a leader in discovering and developing novel immunological agents to treat various cancers, reported a corporate update and provided financial results for the fourth quarter and full year 2023 (Press release, Agenus, MAR 14, 2024, View Source [SID1234641150]).

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"In 2023, Agenus made significant advances across our BOT/BAL development program. Our first target indication is metastatic, refractory colorectal cancer that is not MSI-H/dMMR, for which we are focused on pursuing accelerated approval," said Garo Armen, Ph.D., Chief Executive Officer. "We are also pursuing multiple strategies to capitalize the company through this important path in our efforts to bring BOT and BOT/BAL to the forefront of solid tumor cancer treatment. Our vision is to maximize BOT’s utility to benefit patients in combination with other immune therapies as well as current standards of care for patients with both early and late-stage tumors."

2023 Highlights on Botensilimab

Colorectal Cancer:

•
Received Fast Track designation for patients with metastatic colorectal cancer that is not MSI-H/dMMR and who do not have liver metastases, and who were previously treated with standard combination chemotherapy, anti-VEGF and anti-EGFR if RAS wild type ("refractory MSS mCRC NLM")
•
Completed enrollment of patients with refractory MSS mCRC NLM in a Phase 1 (n=150) and randomized Phase 2 (n=230) in October 2023.
•
Clinical data reported by Agenus in October 2023 revealed:
•
Among the 70 efficacy evaluable ("EE") patients in the refractory MSS mCRC NLM treatment setting, a 24% RECIST v1.1 response rate was observed in those treated with the BOT/BAL combination. Based on literature review, the response rate in a similar population treated with standard of care therapies ranges from 1% to 6.1%1, 2.
•
The 12-month overall survival (OS) rate is 74% with median OS not yet reached.
•
Topline data from the ongoing Phase 2 study are expected in 2H 2024.
•
The most common safety observations are immune-related diarrhea and colitis, which are managed in accordance with standard therapies. Grade 3 treatment related diarrhea/colitis occurred in approximately 14% of patients.

Neoadjuvant CRC:

•
Clinical data presented at ASCO (Free ASCO Whitepaper)-GI January 2024:
•
In an investigator sponsored trial (IST) led by Dr. Pashtoon Kasi at Weill-Cornell Medicine, patients diagnosed with resectable localized colon or rectal cancer were treated with one dose of BOT and two doses of BAL approximately 4 weeks prior to planned surgery. After surgery, pathologic analysis reported significant tumor shrinkage.
•
3/3 patients (100%) with MSI-H CRC experienced major pathological responses (>90% tumor shrinkage) in less than 4 weeks, while 6/9 (67%) MSS CRC patients had tumor shrinkage of 50% or more.
•
IST is expanding to 24 patients with an extended follow-up time (6-8 weeks); Agenus plans to prioritize neoadjuvant development and is evaluating study designs for subsequent pivotal trials.
2L Metastatic Pancreatic:

•
In patients with metastatic pancreatic cancer who have failed or don’t respond to FOLFIRINOX (2L Pancreatic) and received treatment with BOT in combination with gemcitabine+nab-paclitaxel, significant tumor marker reductions were observed in 4 of 5 patients, all with liver metastases.
•
Two (2) of the 4 patients achieved PRs at 16 weeks (target lesion reductions of 47% (confirmed) and -37% (pending confirmation). Two other patients showed stable disease at their first 8-week scan with tumor reductions of -20% and -13%.
•
A Phase 2 randomized study is in progress, with preliminary data expected to be available mid-year.
CTLA-4/PD-1 Relapsed Refractory Advanced Melanoma ("2L+ Melanoma"):

•
Phase 1b expansion cohort in 2L+ Melanoma reported a 30% ORR and 60% disease control rate (n=10; 2/8 BOT responses and 1/2 BOT/BAL responses); all patients had failed anti-PD-1 therapy and 8/10 had failed both anti-PD-1/CTLA-4 therapy.
•
In the Phase 2 study in 2L+ Melanoma, data from the fully enrolled BOT monotherapy arm and a cohort of patients on BOT/BAL (n=30) are anticipated in 2H2024.
Refractory Non-Small Cell Lung Cancer (NSCLC):

•
In the PD(L)-1 refractory cohort, a 56% ORR and an 89% disease control rate were observed in patients treated with the BOT/BAL combination (n=9).
•
In a TKI-refractory cohort, 2 out of 7 patients experienced complete confirmed objective responses after treatment with BOT/BAL.*
Advanced Sarcomas:

•
Updated findings from a Phase 1b study of 41 efficacy evaluable patients treated with BOT/BAL showed durable responses with an ORR of 20%, a median response duration of 19.4 months (iRECIST), and a 6-month progression-free survival rate of 40%.
•
A higher ORR was observed by dose level, with 29% at 2 mg/kg BOT compared to 15% at 1 mg/kg BOT.
Refractory Ovarian:

•
In a total of 24 evaluable patients treated with BOT/BAL, with a median of four prior lines of therapy, an overall response rate of 33% was observed. The disease control rate was 67% and the median Duration of Response (DOR) was not yet reached.
Finance

•
$25 million milestone payment from BMS triggered by the commencement of a Phase 2 study with BMS-986442 in December 2023.
•
Advancing in our discussions on monetizing non-strategic assets, royalty monetization, and project financing, with the potential to yield $100-200 million in cash proceeds.
•
Currently we are in active discussions with several potential biopharma partners for potential co-development and co-commercialization of BOT/BAL.

Fourth Quarter and Full Year 2023 Financial Results

For the year ended December 31, 2023, we recognized revenue of $156 million and incurred a net loss of $257 million, or $0.69 per share. For the fourth quarter ended December 31, 2023, we recognized revenue of $84 million and incurred a net loss of $49 million or $0.13 per share. Revenue primarily includes revenue under our collaboration agreements, including milestones achieved, and revenue related to non-cash royalties earned.

We ended the year with a $76.1 million cash balance; subsequent to which in January 2024 we received the $25 million milestone payment from BMS triggered by the commencement of a Phase 2 study with BMS-986442, the AGENUS discovered TIGIT bispecific antibody. Additionally, we’ve progressed in monetizing non-strategic assets and future milestones and royalties from ongoing partnerships. These efforts are expected to yield significant cash proceeds by mid 2024. Accordingly, we anticipate being funded through 2024. In parallel, we’re pursuing potential partnership discussions with several biopharmaceuiticsl parties to further expand our cash resources.

Conference Call

Date: March 14th, 2024, 8:30 a.m. ET

To access dial-in numbers, please register here.

Conference ID: 73242

Webcast

A live webcast and replay of the conference call will be accessible on the company’s website at View Source and via View Source

References

1 Prager et. al NEJM 2023

2 Grothey et al. Lancet 2013

* Investigator reported, subject to change

About Botensilimab

Botensilimab is an investigational multifunctional anti-CTLA-4 immune activator (antibody) designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to "cold" tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses.

Approximately 900 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316.

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.