On November 6, 2024 Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for patients with cancer, reported financial results for the third quarter ended September 30, 2024, and provided a pipeline update on its clinical-stage investigational molecules – targeting TIGIT, HIF-2a, CD73, the A2a/A2b receptors, CD-39, AXL and PD-1 – across multiple common cancers (Press release, Arcus Biosciences, NOV 6, 2024, View Source [SID1234647801]).

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"Through the course of this year, we have presented multiple compelling datasets at medical conferences that we believe have de-risked several programs and support potential best-in-class profiles for our molecules, including our HIF-2a inhibitor casdatifan in ccRCC and our Fc-silent anti-TIGIT antibody domvanalimab in lung and upper gastrointestinal cancers," said Terry Rosen, Ph.D., chief executive officer of Arcus. "Meanwhile, in addition to our rapidly approaching first Phase 3 readout for domvanalimab in gastric cancer, we are aggressively pursuing our development plan for casdatifan, including in the IO-naive ccRCC setting in collaboration with AstraZeneca, and in the post-IO setting with the initiation of our Phase 3 PEAK-1 study in the first half of next year."
Corporate Updates:

•In October 2024, Arcus announced a clinical collaboration with AstraZeneca to evaluate casdatifan in combination with volrustomig, AstraZeneca’s investigational PD-1/CTLA-4 bispecific antibody, in IO-naive patients with ccRCC. AstraZeneca will operationalize the study. This is the second clinical collaboration between Arcus and AstraZeneca. Gilead retains the right to opt in to the development and commercialization for casdatifan after delivery of a qualifying data package.
Pipeline Highlights:

Casdatifan (HIF-2a inhibitor)
Casdatifan Updates:
•First clinical data from the casdatifan 100mg and 50mg expansion cohorts of ARC-20, a Phase 1/1b study in metastatic ccRCC, were presented in an oral plenary session at the 2024 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium in October. Observations from the 100mg daily expansion cohort included:
◦An objective response rate (ORR) of 34% (2 responses are pending confirmation; 25% confirmed ORR), a low rate of primary progression of 19% and a high disease control rate of 81%.
◦The median progression-free survival (PFS) had not been reached at the time of the data cutoff.

◦Together, these data support the potential for casdatifan to be a best-in-class HIF-2a inhibitor for the treatment of ccRCC.
•In the third quarter, Arcus had a successful Type B meeting with the U.S. Federal Drug Administration (FDA) to discuss its first Phase 3 study for casdatifan, PEAK-1, which will evaluate casdatifan in combination with cabozantinib versus cabozantinib in post-IO patients with ccRCC. Arcus is moving rapidly toward the initiation of PEAK-1 in the first half of 2025.
Upcoming Casdatifan Milestones:
•Multiple expansion cohorts of ARC-20 evaluating casdatifan in ccRCC as a monotherapy and in combination with cabozantinib in ccRCC are underway with additional data presentations expected in the next 12 months.
◦100mg (50mg twice daily (BID), capsules) and 50mg expansion cohorts: Updated data, including median PFS, are expected to be presented in the first quarter of 2025.
◦150mg and 100mg (once daily (QD), tablets) expansion cohorts: Initial data are expected to be presented in 2025.
◦100mg of casdatifan plus cabozantinib: Safety data are expected to be presented in 2025.
Domvanalimab (Fc-silent anti-TIGIT antibody) plus Zimberelimab (anti-PD-1 antibody)
Domvanalimab-Zimberelimab Updates:
•Data from Part 1 of ARC-10, a randomized study evaluating domvanalimab plus zimberelimab in PD-L-1 high NSCLC are being presented at the SITC (Free SITC Whitepaper) Annual Meeting in November.
•Domvanalimab plus zimberelimab was associated with greater PFS, overall survival, and objective response rate compared with zimberelimab or chemotherapy.
◦A 36% reduction in risk of death (hazard ratio [HR]=0.64) was observed for domvanalimab plus zimberelimab compared to that of zimberelimab alone.
◦Zimberelimab reached a median overall survival of 2 years, and the median overall survival for domvanalimab plus zimberelimab was not reached.
◦Treatment-related adverse events leading to treatment discontinuation were low (10.5%) for the combination of domvanalimab and zimberelimab.
•Data from an investigator-sponsored trial evaluating domvanalimab plus zimberelimab in anti-PD-(L)1 refractory hepatocellular carcinoma will be presented in an oral session at the SITC (Free SITC Whitepaper) Annual Meeting.
Upcoming Domvanalimab-Zimberelimab Milestones:
•Overall survival data from the Phase 2 EDGE-Gastric study, evaluating domvanalimab plus zimberelimab and chemotherapy in upper gastrointestinal (GI) adenocarcinomas, are expected to be presented in 2025.

CD73-Adenosine Axis: Quemliclustat (small-molecule CD73 inhibitor) and Etrumadenant (A2a/A2b receptor antagonist)

Quemliclustat
•Arcus has initiated PRISM-1, a Phase 3 trial of quemliclustat combined with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in pancreatic cancer.
Etrumadenant
•Biomarker data from cohort B of ARC-9, a randomized Phase 1b/2 study evaluating etrumadenant plus zimberelimab, FOLFOX chemotherapy and bevacizumab (EZFB) versus regorafenib in third-line metastatic colorectal cancer (mCRC), are being presented at SITC (Free SITC Whitepaper) in November.

Early Clinical Programs

•Evaluation of AB801, a potent and highly selective small-molecule AXL inhibitor, in the dose-escalation phase of a Phase 1/1b study in patients is ongoing. Arcus anticipates advancing this molecule into expansion cohorts in NSCLC in early 2025.
Financial Results for Third Quarter 2024:
•Cash, Cash Equivalents and Marketable Securities were $1.1 billion as of September 30, 2024, compared to $866 million as of December 31, 2023. The increase during the period is primarily due to the receipt of $320 million in cash from Gilead for their January 2024 equity investment, the receipt of the $100 million option continuation payment from Gilead in July 2024 and proceeds from our $50 million term loan, partially offset by the use of cash in research and development activities. We believe our cash, cash equivalents and marketable securities on-hand will be sufficient to fund operations into mid-2027. Cash, cash equivalents and marketable securities are expected to be between $950 million and $985 million at the end of 2024.
•Revenues were $48 million for the third quarter 2024, compared to $32 million for the same period in 2023. In the third quarter 2024, Arcus recognized $41 million in license and development services revenue related to the advancement of programs and Taiho’s exercise of its option for the license of quemliclustat for the Taiho Territory of $15 million, as well as $7 million in other collaboration revenue primarily related to Gilead’s ongoing rights to access Arcus’s research and development pipeline in accordance with the Gilead collaboration agreement.
•Research and Development (R&D) Expenses were $123 million for the third quarter 2024, compared to $82 million for the same period in 2023. The net increase of $41 million was primarily driven by higher clinical trial and headcount-related costs associated with our late-stage development program activities. Non-cash stock-based compensation expense was $9 million for the third quarter 2024, compared to $8 million for the same period in 2023. For the third quarter 2024 and 2023, Arcus recognized gross reimbursements of $37 million and $33 million, respectively, for shared expenses from its collaborations, primarily the Gilead collaboration. R&D expense by quarter may fluctuate due to the timing of clinical manufacturing and standard-of-care therapeutic purchases with a corresponding impact on reimbursements.
•General and Administrative (G&A) Expenses were flat for the third quarter 2024, compared to the same period in 2023. Non-cash stock-based compensation expense was $10 million for each of the third quarter 2024 and 2023.
•Net Loss was $92 million for the third quarter 2024, compared to $71 million for the same period in 2023.
Conference Call Information:
Arcus will host a conference call and webcast today, November 6, at 2:00 PM PT / 5:00 PM ET to discuss its third-quarter 2024 financial results and pipeline updates. To access the call, please dial +1 (404) 975-4839 (local) or +1 (833) 470-1428 (toll-free), using Access Code: 940081. Participants may also register for the call online using the following link: View Source;confId=72838. To access the live webcast and accompanying slide presentation, please visit the "Investors & Media" section of the Arcus Biosciences website at www.arcusbio.com. A replay of the webcast will be available following the live event.
Arcus Ongoing and Announced Clinical Studies:
Trial Name Arms Setting Status NCT No.
Lung Cancer
STAR-121 dom + zim + chemo vs. pembro + chemo 1L NSCLC (PD-L1 all-comers) Ongoing Registrational Phase 3
NCT05502237
PACIFIC-8 dom + durva vs. durva Unresectable Stage 3 NSCLC Ongoing Registrational Phase 3
NCT05211895
ARC-7 zim vs. dom + zim vs. etruma + dom + zim 1L NSCLC (PD-L1 ≥ 50%) Ongoing Randomized Phase 2
NCT04262856
EDGE-Lung dom +/- zim +/- quemli +/- chemo 1L/2L NSCLC (lung cancer platform study) Ongoing Randomized Phase 2
NCT05676931
VELOCITY-Lung
dom +/- zim +/- etruma +/- sacituzumab govitecan-hziy or other combos
1L/2L NSCLC (lung cancer platform study) Ongoing Randomized Phase 2
NCT05633667
Upper Gastrointestinal Cancers
STAR-221 dom + zim + chemo vs. nivo + chemo 1L Gastric, GEJ and EAC Ongoing Registrational Phase 3
NCT05568095
EDGE-Gastric (ARC-21) dom +/- zim +/- quemli +/- chemo 1L/2L Upper GI Malignancies
Ongoing
Randomized Phase 2
NCT05329766
Colorectal Cancer

ARC-9 etruma + zim + mFOLFOX vs. SOC 2L/3L/3L+ CRC
Ongoing
Randomized Phase 2
NCT04660812
Pancreatic Cancer
PRISM-1 quemli + gem/nab-pac vs. gem/nab-pac 1L PDAC Ongoing Phase 3
NCT06608927
ARC-8 quemli + zim + gem/nab-pac vs. quemli + gem/nab-pac 1L, 2L PDAC Ongoing Randomized Phase 1/1b
NCT04104672
Kidney Cancer
PEAK-1 cas + cabo vs. cabo Post-IO ccRCC Planned Phase 3 TBD
ARC-20 cas, cas + cabo Cancer Patients / ccRCC Ongoing Phase 1/1b
NCT05536141
Other
ARC-25 AB598 Advanced Malignancies Ongoing
NCT05891171
ARC-27 AB801 Advanced Malignancies Ongoing
NCT06120075

cabo: cabozantinib; cas: casdatifan; dom: domvanalimab; durva: durvalumab; etruma: etrumadenant; gem/nab-pac: gemcitabine/nab-paclitaxel; nivo: nivolumab; pembro: pembrolizumab; quemli: quemliclustat; SOC: standard of care; zim: zimberelimab; ccRCC: clear cell renal cell carcinoma; CRC: colorectal cancer; EAC: esophageal adenocarcinoma; GEJ: gastroesophageal junction; GI: gastrointestinal; NSCLC: non-small cell lung cancer; PDAC: pancreatic ductal adenocarcinoma.

On November 6, 2024 Anixa Biosciences, Inc. ("Anixa" or the "Company") (NASDAQ: ANIX), a biotechnology company focused on the treatment and prevention of cancer, reported that the presentation of additional data from the Phase 1 clinical trial of its breast cancer vaccine at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting, will be made publicly available on the Company’s website at 12:15pm CT on November 8, 2024 (Press release, Anixa Biosciences, NOV 6, 2024, View Source [SID1234647800]). Concurrently, the Company will issue a press release providing an analysis of the data.

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As previously announced, the presentation, titled "Phase I Trial of alpha-lactalbumin vaccine in high risk operable triple negative breast cancer (TNBC) and patients at high genetic risk for TNBC," will be presented at 12:15pm CT on November 8, 2024 at the SITC (Free SITC Whitepaper) 39th Annual Meeting.

The poster presentation can be viewed starting at 12:15pm CT on November 8, 2024 at View Source

On November 6, 2024 Alligator Bioscience (Nasdaq Stockholm: ATORX), a company developing CD40 agonists to treat cancer, reported the presentation of positive Phase 2 data on its lead drug candidate mitazalimab in 1st line pancreatic cancer at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC 2024), taking place November 6-10 in Houston, TX (Press release, Alligator Bioscience, NOV 6, 2024, View Source [SID1234647799]).

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The poster presentation, entitled "CD40 agonist mitazalimab combined with mFOLFIRINOX in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): Updated efficacy and correlative biomarkers from the OPTIMIZE-1 trial", outlined updated efficacy and biomarker analysis from 57 evaluable patients treated with the 900 µg/kg dose in the OPTIMIZE-1 study.

The confirmed overall response rate (ORR) was 42.1%, with 23 partial responses (PR) and one complete response (CR). The ORR including unconfirmed responses was 54.4%. Median overall survival (OS) was 14.9 months, with a near doubling of the 18-month OS rate to 36.2%, compared to 18.6% reported with FOLFIRINOX[1] alone. Median duration of response (DoR) was 12.6 months, an unprecedented outcome in this aggressive disease, and median progression free survival (PFS) was 7.7 months. A total of 19 patients (33%) remained in the study, with nine still undergoing treatment.

Furthermore, changes in immunological profiles observed after the priming dose of mitazalimab and before the first dose of mFOLFIRINOX correlated with improved efficacy outcomes, suggesting a mitazalimab-driven response in this novel regimen. These data form the basis of a future randomized confirmatory trial of mitazalimab in combination with mFOLFIRINOX in mPDAC.

Alligator also had a poster presentation on ATOR-4066, its next-generation bispecific CD40 antibody candidate that targets CD40 and CEACAM5. The results showed that ATOR-4066 induces both myeloid cell-dependent and T-cell dependent anti-tumor activity in preclinical models. The strong in-vivo anti-tumor activity indicates the potential of ATOR-4066 as a monotherapy or in combination with other anticancer agents, in particular immune checkpoint inhibitors (ICI), to overcome ICI resistance in CEACAM5-expressing tumors.

Dr. Sumeet Ambarkhane, CMO at Alligator Bioscience, said: "We are proud to present these positive data, both Phase 2 on mitazalimab and preclinical on exciting bispecific CD40 antibody candidate ATOR-4066, to the scientific community at SITC (Free SITC Whitepaper) 2024. The results demonstrate the potential of these candidates to significantly improve treatment options for patients, and confirm our CD40 agonists as the primary value drivers for Alligator. The OPTIMIZE-1 Phase 2 data, in particular, are very exciting as these show mitazalimab increases the chance of being alive after 18 months by 95 percent compared to the current standard of care chemotherapy, FOLFIRINOX. This clinically meaningful survival benefit shows the potential of mitazalimab to make a significant difference for pancreatic cancer patients, who still sadly have very poor prognosis."
Mitazalimab is a stimulatory monoclonal antibody that selectively targets CD40, a receptor on dendritic cells; these specialized immune cells are capable of unveiling cancer cells to the body’s immune system. In other words, CD40 stimulation enables dendritic cells to more effectively activate the immune system’s weapons – specifically, T cells – and to direct them to attack the unveiled cancer cells. Data from the Phase 2 OPTIMIZE-1 clinical trial, first announced in June 2024, showed mitazalimab caused an unprecedented duration of response in first-line pancreatic cancer patients, nearly doubling 18-month survival rates. As expected based on its mechanism of action, preclinical results have shown that mitazalimab also may be effective against several additional types of cancer.

ATOR-4066, in preclinical development, is an advancement on the mechanism of mitazalimab. It is a CD40 bispecific antibody targeting both CD40 and CEA (carcinoembryonic antigen), a protein found in certain tumors but not in normal tissue. This approach is expected to improve both safety and anti-tumor efficacy.

On November 6, 2024 Aligos Therapeutics, Inc. (Nasdaq: ALGS, "Aligos"), a clinical stage biopharmaceutical company focused on improving patient outcomes through best-in-class therapies for liver and viral diseases, reported recent business progress and financial results for the third quarter 2024 (Press release, Aligos Therapeutics, NOV 6, 2024, View Source [SID1234647798]).

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"This quarter we reached a key milestone when we announced the positive topline HERALD data in MASH subjects," stated Lawrence Blatt, Ph.D., MBA, Chairman, President, and Chief Executive Officer of Aligos Therapeutics. "With placebo-adjusted median relative reductions in liver fat of up to 46.2%, we continue to believe ALG-055009 has best-in-class potential. We are completing Phase 2b enabling studies and evaluating a variety of options to fund continued development, including potential partnering where discussions are underway. In addition, we are progressing ALG-000184 for CHB towards a Phase 2 study next year. Lastly, we expect to begin externally funded clinical studies for ALG-097558 later this year in COVID subjects. 2024 has been an exciting year for the company, and we believe we are laying the groundwork for important future successes in 2025 and beyond."

Recent Business Progress

Aligos Portfolio of Drug Candidates

ALG-000184: Potential first-/best-in-class small molecule CAM-E for CHB

Dosing continues in this ongoing Phase 1a/1b study, with subjects expected to dose for up to 96 weeks. Additional interim data readouts are planned to be presented this year at the American Association for the Study of Liver Disease’s (AASLD) The Liver Meeting (TLM) 2024
Received positive feedback from the FDA and the National Medical Products Administration in China to move forward with sustained HBV DNA suppression as the primary efficacy endpoint for future studies designed to support the potential registration of ALG-000184 for the treatment of hepatitis B infection
Announced a clinical collaboration with Xiamen Amoytop Biotech Co., Ltd.
Amoytop agreed to sponsor and perform a Phase 1b exploratory clinical study evaluating the efficacy and safety of ALG-000184 in combination with PEGBING (mipeginterferon alfa-2b) in chronic hepatitis B (CHB) patients in China
Phase 2 enabling activities are underway, including drug supply manufacturing
ALG-055009: Potential best-in-class small molecule THR-β agonist for MASH

Topline HERALD data were presented in September 2024, demonstrating that ALG-055009 dose groups met the primary endpoint with statistically significant reductions in liver fat at Week 12 as measured by MRI-PDFF
Doses of 0.5 mg to 0.9 mg ALG-055009 demonstrated statistically significant reductions in liver fat at Week 12, with placebo-adjusted median relative reductions up to 46.2% as measured by MRI-PDFF. Up to 70% of subjects achieved ≥30% relative reduction in liver fat compared to baseline
ALG-055009 demonstrated a favorable tolerability profile with no clinical hyper/hypothyroidism. Incidence of gastrointestinal-related treatment emergent adverse events were similar in ALG-055009 dose groups compared to placebo. Specifically, a non-dose-related, lower incidence of diarrhea was observed in ALG-055009 dose groups compared to placebo
Treatment with ALG-055009 resulted in significant reductions in atherogenic lipids, including LDL-C, lipoprotein (a) (LpA), and apolipoprotein B (ApoB). In addition, dose dependent increases in sex hormone binding globulin (SHBG), a marker of THR-β target engagement in the liver, were observed
Additional data readouts are planned to be presented this year at AASLD’s The Liver Meeting (TLM) 2024
ALG-097558: Potential best-in-class small molecule pan-coronavirus protease inhibitor

Three additional clinical studies are expected to begin in 2024
AGILE University of Liverpool, a UK-government supported platform trial (with MRC and Wellcome Trust funding), has agreed to sponsor and perform a study in high-risk COVID patients evaluating ALG-097558 as monotherapy or in combination with remdesivir
The NIAID has agreed to sponsor clinical studies evaluating pharmacokinetic (PK) differences in special populations (renal/hepatic impairment subjects)
Phase 2 enabling activities, including nonclinical and clinical studies, are underway with financial support from the NIH
Financial Results for the Third Quarter 2024

Cash, cash equivalents and investments totaled $74.9 million as of September 30, 2024, compared with $135.7 million as of December 31, 2023. We continue to believe our cash balance provides sufficient cash to fund planned operations through the end of 2025.

Net loss for the three months ended September 30, 2024 were $19.3 million or basic and diluted net loss per common share of $(3.07), compared to net losses of $18.0 million or basic and diluted net loss per common share of $(10.37) for the three months ended September 30, 2023.

Research and development (R&D) expenses for the three months ended September 30, 2024 were $16.8 million, compared with $15.9 million for the same period of 2023. The increase was primarily due to an increase in third party expenses for the clinical trials. Total R&D stock-based compensation expense incurred for the three months ended September 30, 2024 was $1.2 million, compared with $1.6 million for the same period of 2023.

General and administrative (G&A) expenses for the three months ended September 30, 2024 were $4.6 million, compared with $6.4 million for the same period of 2023. The decrease in G&A expenses for this comparative period is primarily due to a decrease in third party expenses including legal expenses. Total G&A stock-based compensation expense incurred for the three months ended September 30, 2024 was $0.9 million, compared with $1.6 million for the same period of 2023.

Interest and other income, net, for the three months ended September 30, 2024 was income of $1.0 million compared with income of $1.1 million for the same period of 2023.

On November 6, 2024 Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company pioneering immuno-neurology, reported third quarter 2024 financial results and recent portfolio and business updates (Press release, Alector, NOV 6, 2024, View Source [SID1234647797]). As of September 30, 2024, Alector’s cash, cash equivalents, and investments totaled $457.2 million.

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"We continue to make meaningful progress advancing our innovative pipeline of product candidates and remain on track to report data in 2024 from the INVOKE-2 Phase 2 trial of AL002, the most advanced TREM2 candidate in clinical development for early Alzheimer’s disease," said Arnon Rosenthal, Ph.D., Chief Executive Officer of Alector. "We believe that increased TREM2 signaling via AL002 may recruit disease-fighting microglia to broadly counteract the progression of Alzheimer’s disease. INVOKE-2 is designed to provide meaningful insights into AL002’s potential benefits across a combination of clinical and functional endpoints, as well as imaging and fluid biomarkers. We also believe that the broad mechanism of AL002 may have the potential to deliver potent and durable therapeutic benefits, both as a standalone therapy and in combination with anti-amyloid beta antibodies."

Dr. Rosenthal continued, "For our progranulin franchise, we recently reported the patient baseline characteristics for our INFRONT-3 Phase 3 clinical trial of latozinemab in frontotemporal dementia with a progranulin gene mutation, suggesting a representative study population in this indication. We are approaching a top-line data readout for INFRONT-3 in late 2025/early 2026. Additionally, PROGRESS-AD, the Phase 2 trial of AL101/GSK4527226 in early Alzheimer’s disease, has reached more than one-third of its target enrollment. It is an exciting time at Alector, and we are well positioned to advance our proprietary pipeline of novel immuno-neurology drugs."

Sara Kenkare-Mitra, Ph.D., President and Head of Research and Development at Alector, added, "We are actively advancing our Alector Brain Carrier, ABC, a proprietary versatile blood-brain barrier technology, and we are strategically leveraging this platform across our portfolio. We believe our ABC technology may advance treatment of neurodegenerative diseases by potentially enabling improved delivery of our therapeutics to the brain."

Recent Clinical Updates

Immuno-Neurology Portfolio
TREM2 Program (AL002) Being Developed in Collaboration with AbbVie

The results of the INVOKE-2 Phase 2 clinical trial of AL002 are expected in 2024. INVOKE-2, a randomized, double-blind, placebo-controlled, dose-ranging study, is designed to assess the efficacy and safety of AL002 in slowing disease progression in individuals with early Alzheimer’s disease (AD). AL002 is a novel investigational humanized monoclonal antibody (mAb) that is designed to bind to TREM2 to increase TREM2 signaling and, thereby, is hypothesized to improve the functionality of microglia. It is the most advanced TREM2 agonist product candidate in clinical development worldwide.
98% of eligible participants who completed the planned treatment period of INVOKE-2 have elected to participate in the long-term extension (LTE) study.
In October 2024, Alector published a manuscript titled "Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer’s disease" in Alzheimer’s Research & Therapy. The publication outlines preclinical and INVOKE-1 Phase 1 study results, demonstrating that AL002 engaged TREM2, and induced pharmacodynamic biomarker changes associated with microglial proliferation, survival, and phagocytic activity in a dose-dependent manner.
AbbVie has an exclusive option to globally develop and commercialize AL002. Alector will deliver a data package resulting from the INVOKE-2 study to AbbVie for their evaluation. AbbVie’s exercise of its option would prompt a $250 million payment to Alector.
Progranulin Programs (latozinemab (AL001) and AL101/GSK4527226) Being Developed in Collaboration with GSK

The pivotal, randomized, double-blind, placebo-controlled INFRONT-3 Phase 3 clinical trial of latozinemab targeting frontotemporal dementia with a progranulin gene mutation (FTD-GRN) is ongoing and on track, with enrollment completed in October 2023 and a treatment duration of 96 weeks. Latozinemab is a novel investigational human mAb that aims to increase progranulin (PGRN) levels by inhibiting sortilin and is the most advanced PGRN-elevating candidate in development for the treatment of FTD-GRN.
In September 2024, Alector presented a poster highlighting the patient baseline characteristics for INFRONT-3 at the 14th International Conference on Frontotemporal Dementias (ISFTD 2024). Notably, the baseline characteristics of symptomatic INFRONT-3 participants, including age, Clinical Dementia Rating scale plus National Alzheimer’s Disease Coordinating Center Frontotemporal Lobar Degeneration Sum of Boxes (CDR plus NACC FTLD-SB) score and neurofilament light chain (NfL) levels, were representative of the broader FTD-GRN registry population, based on available registry data. Additionally, Alector shared findings from the FTD Caregiver Survey and FTD Insights Survey, highlighting the challenges faced by caregivers of individuals living with FTD.
PROGRESS-AD, a global, randomized, double-blind, placebo-controlled Phase 2 clinical study evaluating AL101/GSK4527226 in early AD has reached more than one-third of its target enrollment of 282 participants, with dosing initiated in February 2024. AL101 is an investigational human mAb designed to block and downregulate the sortilin receptor to elevate the level of PGRN in the brain in a manner that is similar to investigational latozinemab but with different pharmacokinetic and pharmacodynamic properties.
Early Research Pipeline

Alector continues to advance its Alector Brain Carrier (ABC), a proprietary, versatile blood-brain barrier technology platform, which is being applied selectively to the company’s next-generation product candidates and research pipeline. The technology platform enables customization of affinity, valency, and format to optimize effector function and half-life in preclinical models. Alector is applying its ABC technology, combined with its expertise in immuno-neurology, to work on novel targets and develop first or best-in-class therapeutics.
Third Quarter 2024 Financial Results

Revenue. Collaboration revenue for the quarter ended September 30, 2024, was $15.3 million, compared to $9.1 million for the same period in 2023. The increase was mainly due to an increase in revenue recognized for the AL002 program.

R&D Expenses. Total research and development expenses for the quarter ended September 30, 2024, were $48.0 million, compared to $46.3 million for the quarter ended September 30, 2023. The increase was mainly driven by the increase in research and development expenses for the AL101 programs resulting from the initiation of the PROGRESS-AD Phase 2 clinical trial in 2024.

G&A Expenses. Total general and administrative expenses for the quarter ended September 30, 2024, were $15.8 million, compared to $13.4 million for the quarter ended September 30, 2023. The increase was mainly due to the impairment of the right-of-use asset and the leasehold improvements as the Company transitioned operations from its laboratory and office space in Newark to its South San Francisco headquarters.

Net Loss. For the quarter ended September 30, 2024, Alector reported a net loss of $42.2 million, or $0.43 per share, compared to a net loss of $44.5 million, or $0.53 per share, for the same period in 2023.

Cash Position. Cash, cash equivalents, and investments were $457.2 million as of September 30, 2024. Management expects that this will be sufficient to fund current operations through 2026.

2024 Guidance. The Company continues to anticipate collaboration revenue to be between $60 million and $70 million, total research and development expenses to be between $210 million and $220 million, and total general and administrative expenses to be between $60 million and $70 million.