On October 23, 2023 Aligos Therapeutics, Inc. (Nasdaq: ALGS), a clinical stage biopharmaceutical company focused on developing novel therapeutics to address unmet medical needs in liver and viral diseases, reported that it has entered into a securities purchase agreement for a private placement that is expected to result in gross proceeds of approximately $92 million, before deducting placement agent fees and other expenses, to advance its portfolio of drug candidates (Press release, Aligos Therapeutics, OCT 23, 2023, View Source [SID1234636234]).

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The private placement is being led by a life sciences dedicated investment firm with participation from other new and existing institutional investors including Armistice Capital, Deep Track Capital, EcoR1 Capital and Roche Venture Fund, among others. Also participating in the private placement are certain members of the company’s Board of Directors, including Lawrence M. Blatt, Ph.D., M.B.A, the company’s Chairman and Chief Executive Officer.

Aligos currently expects to use the net proceeds from the private placement, together with its existing cash, cash equivalents and investments, to fund the continued advancement of its Phase 2a NASH, ALG-055009 study evaluating its thyroid hormone receptor beta agonist, its CAM-E candidate, ALG-000184, as well as to fund discovery and research to broaden its pipeline of drug candidates, and for other general corporate purposes.

Aligos believes its cash, cash equivalents and investments, including the expected net proceeds from the private placement, will provide sufficient funding of planned operations through the end of 2025.

In the private placement, Aligos is selling 31,429,266 shares of common stock, pre-funded warrants to purchase up to 81,054,686 shares of common stock and accompanying warrants to purchase up to 56,241,973 shares of common stock, at a combined price of $0.8193 per share of common stock and accompanying warrant and $0.8192 per pre-funded warrant and accompanying warrant. Each pre-funded warrant will have a nominal exercise price of $0.0001 per share of common stock, will be immediately exercisable and will be exercisable until exercised in full. The accompanying warrants will have an exercise price of $0.7568 per share of common stock, will be immediately exercisable and will expire on October 25, 2030. The private placement is expected to close on October 25, 2023, subject to the satisfaction of customary closing conditions.

Piper Sandler is acting as sole placement agent for the private placement.

The securities sold in this private placement have not been registered under the Securities Act of 1933, as amended, or applicable state securities laws, and may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements. Aligos has agreed to file a registration statement with the Securities and Exchange Commission registering the resale of the shares of common stock issued in the private placement and the shares of common stock issuable upon exercise of the pre-funded warrants and the common warrants issued in the private placement.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.

On October 23, 2023 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, reported excellent new clinical data from the TACTI-002 / KEYNOTE-798 Phase II trial evaluating eftilagimod alpha ("efti"), a soluble LAG-3 protein and first-in-class MHC Class II agonist, in combination with MSD’s (Merck & Co., Inc., Rahway, NJ., USA) anti-PD-1 therapy KEYTRUDA (pembrolizumab) as first-line treatment for patients with previously untreated unresectable or metastatic non-small cell lung cancer (NSCLC) (Press release, Immutep, OCT 23, 2023, View Source [SID1234636220]).

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The updated TACTI-002 data, with a cut-off date of August 15, 2023 and a median follow up of over 2 years (25.1 months), was presented by Dr. Enric Carcereny, Catalan Institute of Oncology (ICO), Badalona, Spain, during a Mini Oral session (#1312MO) at ESMO (Free ESMO Whitepaper) Congress 2023 on Saturday, October 21st. Key takeaways from the oral presentation detailing results from efti in combination with KEYTRUDA for frontline treatment of advanced or metastatic NSCLC in the TACTI-002 Phase II trial1 include:

Promising Overall Survival (OS), Overall Response Rate (ORR), Progression Free Survival (PFS), and Duration of Response (DOR) are visible across all PD-L1 subgroups (Tumor Proportion Score [TPS] <1%, ≥1%, 1-49%, and ≥50%), which clearly differentiates efti in combination with KEYTRUDA from other chemo-free immuno-oncology (IO) combinations for first-line treatment of NSCLC.
A significant overall survival benefit was achieved, with a 35.5-month median Overall Survival (mOS) in patients with TPS ≥1%, 23.4-month mOS in TPS 1-49%, and mOS not yet reached in TPS ≥50%. Notably, the mOS in TPS ≥1% was attained with central assessment of PD-L1 (N=58) and a larger patient group with central + local assessment of PD-L1 (N=71), and the 35.5-month mOS compares very favourably to standard-of-care IO, IO-IO, IO-chemo, and IO-IO-chemo therapies (Table 1).
Exceptional durability and quality of responses are increasingly evident with strong overall survival (OS) and progression free survival (PFS) rates across patients expressing PD-L1. The 3-year OS rates are 45.6%, 31.0%, and 63.6% in TPS ≥1%, TPS 1-49%, and TPS ≥50%, respectively. The 12-month PFS rates are 46.8%, 42.1%, and 55.0% for TPS ≥1%, TPS 1-49%, and TPS ≥50%, respectively.
The entire patient population regardless of PD-L1 expression (N=114) showed encouraging efficacy with 20.2-month mOS, 21.6-month mDoR, and a 36-month OS rate of 36% despite ~75% of patients having negative or low PD-L1 expression.
Table 1: Overall Survival of Efti + KEYTRUDA versus standard-of-care IO, IO-IO, IO-chemo, and IO-IO-chemo
therapies for first-line treatment of advanced non-small cell lung cancer patients with PD-L1 TPS ≥1%

Therapy Median Overall Survival2
Efti + Pembrolizumab 35.5 months
Pembro + Doublet Chemo (NSQ)* 23.3 months
Pembro + Doublet Chemo (SQ)* 18.9 months
Ipilimumab + Nivolumab3 17.1 months
Pembrolizumab monotherapy3 16.4 months
Ipi + Nivo + 2 cycles Doublet Chemo 15.8 months
* NSQ=Non-squamous; SQ=Squamous

In NSCLC patients with ≥1% PD-L1 expression, a key area for efti’s future development where it has FDA Fast Track status, the ORR (48.3%), mPFS (11.2 months), mDOR (24.2 months), and mOS (35.5 months) compare overall favourably to historical results of anti-PD-1 monotherapy, as well as to historical results of approved anti-PD-1 + chemo-containing regimens. Collectively, the breadth of efficacy and safety data from the large number of metastatic NSCLC patients in the Phase II TACTI-002 trial offers compelling evidence of efti’s substantial impact in safely stimulating the patients’ immune response to fight cancer.

Dr. Enric Carcereny stated, "The strong efficacy data across all levels of PD-L1 expression in TACTI-002, especially in PD-L1 low (1-49%) and PD-L1 negative (<1%) patients, differentiates efti in combination with anti-PD-1 from other chemo-free immuno-oncology combinations in the frontline treatment of advanced or metastatic non-small cell lung cancer. Unlike other IO-IO combinations that only work in high PD-L1 expressing patients or IO-chemo combinations that rely on toxic chemotherapy to drive better efficacy, efti is clearly enabling deep, durable responses for patients regardless of PD-L1 expression with a favourable safety profile that’s in line with anti-PD-1 monotherapy."

Marc Voigt, Immutep CEO stated, "We are extremely pleased to report these excellent overall survival results, the gold standard benchmark within oncology, in patients with metastatic non-small cell lung cancer, and believe these are among the strongest ever delivered in a sizable Phase II clinical trial like TACTI-002 evaluating a dual immuno-oncology approach. The strength of the data positions us well as we continue to plan and prepare for our Phase III trial that we expect to launch next year."

Conference Call and Webcast Details
Immutep will host a conference call and webcast to discuss the clinical data presented at ESMO (Free ESMO Whitepaper) 2023 and provide an overview on future clinical development plans for efti in 1st line non-small cell lung cancer. The event will feature CEO Marc Voigt, CSO Dr Frederic Triebel, CMO Dr Florian Vogl, and Christian Mueller, Senior Vice President Strategic Development. An open question & answer session with all presenters will conclude the event. A replay of the webcast will be available under the Events section of Immutep’s website.

Date/Time: Monday, October 23rd, at 8AM AEDT (Sunday, October 22nd, at 5PM ET)
Register: Link to register here.
Questions: Investors are invited to submit questions in advance via [email protected].

Lung cancer is the second most common cancer. Non-small cell lung cancer accounts for approximately 80-85% of all lung cancers, impacting an estimated 1.87 million people annually, and is the highest cause of death among all cancers4-6.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About Eftilagimod Alpha (Efti)
Efti is Immutep’s proprietary soluble LAG-3 protein and MHC Class II agonist that stimulates both innate and adaptive immunity for the treatment of cancer. As a first-in-class antigen presenting cell (APC) activator, efti binds to MHC (major histocompatibility complex) Class II molecules on APC leading to activation and proliferation of CD8+ cytotoxic T cells, CD4+ helper T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-ƴ and CXCL10 that further boost the immune system’s ability to fight cancer.

Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy. Efti has received Fast Track Designation in 1st line HNSCC and in 1st line NSCLC from the United States Food and Drug Administration (FDA).

On October 22, 2023 Personalis, Inc. (Nasdaq: PSNL), a leader in precision oncology, reported the presentation of initial findings from its work with the groundbreaking TRACERx lung cancer study, marking a substantial advancement in lung cancer circulating tumor DNA (ctDNA) detection and management (Press release, Personalis, OCT 22, 2023, View Source [SID1234636232]). The Personalis NeXT Personal cancer assay, created to detect and monitor residual and recurrent disease (MRD), demonstrated significantly improved detection rates for early-stage lung cancer, including lung adenocarcinoma (LUAD), one of the most common and challenging subtypes of non-small cell lung cancer (NSCLC) to identify in blood samples.

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The findings come from an analysis by Professor Charles Swanton, Dr. James Black, and other members of the TRACERx consortium, renowned for their work on the complexities of cancer genomics. The findings were presented by Dr. Black at the 2023 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress on October 21 in Madrid, Spain, and are the first publicly presented results from Personalis’ collaboration with Cancer Research UK’s Cancer Research Horizons, University College London (UCL), and the Francis Crick Institute.

Lung cancer is the second most common cancer in the U.S., with an estimated 238,000 new cases and approximately 127,000 deaths forecasted for 2023. The current standard of care for relapse detection of NSCLC, the most common type of lung cancer, is primarily focused on imaging modalities such as CT scans, which are known to be limited in sensitivity. This ongoing collaboration is focused on addressing this challenge through advanced ctDNA analysis. For the current analysis, the teams used NeXT Personal to identify and track MRD in over 170 patients from the TRACERx cohort.

Higher sensitivity for early-stage lung cancer

In this analysis, NeXT Personal showed significantly higher sensitivity in early-stage NSCLC patients compared to two previous publications on the TRACERx cohort. Pre-surgery, the assay demonstrated 100% sensitivity for ctDNA in pre-surgical non-LUAD samples and 81% pre-surgical ctDNA sensitivity for LUAD, one of the most common types of lung cancer but also one of the most challenging to detect in blood. The pre-surgical sensitivity for early-stage LUAD was up to 4X higher than in previous studies on the TRACERx cohort, depending on stage. This high sensitivity enhanced the assay’s ability to detect recurrence and monitor lung cancer effectively.

Ability to identify low and high recurrence risk prior to surgery

The study demonstrated that pre-surgical ctDNA levels with NeXT Personal could be used to classify early-stage lung cancer patients into lower- and higher-recurrence risk groups. Furthermore, the analysis showed that the ultra-low levels of ctDNA detection enabled by NeXT Personal were critical to determining patient recurrence risk. For example, LUAD patients who were ctDNA-negative before surgery with NeXT Personal strikingly exhibited a 100% 5-year overall survival rate and 94% relapse-free survival rate in the TRACERx cohort. In comparison, patients who were ctDNA-positive prior to surgery had a high risk of cancer recurrence over 5 years.

Earlier detection for earlier potential intervention

The results presented at ESMO (Free ESMO Whitepaper) also showed that NeXT Personal enabled earlier detection of residual or recurrent lung cancer after surgery in the TRACERx cohort. The results show a median lead time of approximately 6 to 11 months for ctDNA detection ahead of traditional imaging, and significantly longer than previous TRACERx results. The ability to identify potential recurrence months earlier offers the possibility to intervene and accelerate treatment in high-risk patients.

The promise of helping lung cancer patients throughout their journey

Overall, the TRACERx results raise the potential of using NeXT Personal to help inform patient management throughout the patient journey, from pre-surgery to post-surgery and longer-term monitoring.

"Existing tests for lung cancer patients often fall short in detecting residual or recurrent cancer early. Our NeXT Personal test is designed to change that by being significantly more sensitive. We are thrilled that the TRACERx results presented at ESMO (Free ESMO Whitepaper) demonstrated higher sensitivity for the most common types of early-stage lung cancer, including the most challenging subtypes. That sensitivity translated into a better understanding of recurrence risk for patients, and earlier detection of recurrence. We hope that earlier detection can ultimately be life-saving, offering patients a greater chance at successful treatment," said Richard Chen, MD, MS, Chief Medical Officer and Executive Vice President, R&D of Personalis.

The NeXT Personal technology leverages whole genome sequencing and advanced noise suppression with NeXT SENSE technology to identify a unique genetic signature derived from a patient’s tumor based on up to ~1,800 variants. This unique signature is tracked in the patient’s blood over time to find residual or recurrent cancer, achieving an industry-leading sensitivity of down to ~1 PPM. This enhanced sensitivity offers the potential for earlier recurrence risk assessment and intervention, earlier detection, more precise monitoring, and substantial advancement in lung cancer care.

"Patients often live in fear of undetected cancer leading to a relapse. Our new assay is a transformative leap forward—it’s like turning on a spotlight in a previously dark room. It finds what other tests often miss, providing a new level of certainty and peace of mind. This isn’t just about technology; it’s about giving patients and their families a clearer path forward in their fight against cancer," said Chris Hall, President and CEO of Personalis.

Webcast and Conference Call Information

Personalis will host a conference call on Tuesday, October 24, 2023 at 6:00 a.m. Pacific Time / 9:00 p.m. Eastern Time. The live webinar, which includes presentation slides, can be accessed here, or at View Source A replay of the webinar will be available shortly after the conclusion of the call and will be archived on the company’s website.

On October 22, 2023 Daiichi Sankyo reported updated results from a subgroup analysis of a first-in-human phase 1 trial showed that raludotatug deruxtecan (R-DXd) continues to demonstrate promising clinical activity in patients with heavily pretreated platinum-resistant advanced ovarian cancer (Press release, Daiichi Sankyo, OCT 22, 2023, View Source [SID1234636231]). These data were presented today during a mini-oral session (745MO) at the 2023 European Society for Medical Oncology (#ESMO23).

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Raludotatug deruxtecan is a specifically engineered potential first-in-class CDH6 directed DXd antibody drug conjugate (ADC) being jointly developed by Daiichi Sankyo (TSE: 4568) and Merck & Co., Inc., Rahway, N.J., USA (known as MSD outside of the United States and Canada).

Approximately 70% to 80% of patients diagnosed with ovarian cancer will have a recurrence of disease following standard treatment with platinum-based chemotherapy regimens.1 An estimated 65% to 85% of patients with ovarian cancer have expression of CDH6, which is associated with poor prognosis.2,3

A confirmed objective response rate (ORR) of 46% (95% CI: 32–61) by investigator assessment was observed in the subgroup of 50 patients with measurable ovarian cancer receiving raludotatug deruxtecan (4.8 to 8.0 mg/kg) in the phase 1 trial. One complete response (CR), 22 partial responses (PRs) and four unconfirmed responses were seen. A disease control rate (DCR) of 98% was observed. Median duration of response (DOR) was 11.2 months (95% CI: 3.0-NE) and median progression-free survival (PFS) was 7.9 months (95% CI: 4.4-12.4) as of the data cutoff of July 14, 2023. Responses were observed in patients with a range of tumor CDH6 expression.

"Following treatment with the current standard of care of platinum-based chemotherapy, disease progression in patients with advanced ovarian cancer is inevitable and underscores the need for new treatment options," said Erika Hamilton, MD, Director, Breast Cancer and Gynecologic Cancer Research, Sarah Cannon Research Institute, Nashville, Tennessee. "The response rate seen in these heavily pretreated patients is promising and further study of raludotatug deruxtecan in ovarian cancer is warranted."

The safety profile of raludotatug deruxtecan was consistent with previous reports from the phase 1 trial. Treatment discontinuations due to treatment-emergent adverse events (TEAEs) occurred in 15% of patients. Grade 3 or higher TEAEs occurred in 51.7% of patients. The most common grade > 3 or higher TEAEs occurring in patients were anemia (18.3%), decreased neutrophil count (11.7%), decreased platelet count (5.0%), fatigue (3.3%), nausea (1.7%), vomiting (1.7%), diarrhea (1.7%) and decreased appetite (1.7%). Two grade 2 interstitial lung disease (ILD) events were confirmed as treatment-related by an independent adjudication committee across the 4.8 to 6.4 mg/kg doses. Two grade 5 treatment-related ILD events were reported at the 8.0 mg/kg dose, which has been discontinued as of October 2022.

"In addition to the response rate seen with raludotatug deruxtecan, the median duration of response of 11.2 months and disease control achieved by more than 98% of patients with platinum-resistant advanced ovarian cancer is encouraging," said Mark Rutstein, MD, Global Head, Oncology Clinical Development, Daiichi Sankyo. "We look forward to further evaluation of our CDH6 directed antibody drug conjugate in this population of patients that currently face poor outcomes with limited treatment options."

A majority of patients (91.7%) had platinum-resistant disease with four median prior lines of systemic therapy (range, 1-13) including bevacizumab (68.3%) and a PARP inhibitor (65%). The median follow-up for DOR was 5.8 months (range, 1.4-16.8) and the median follow-up for PFS was 5.6 months (range, 0.03-25.1). The median treatment duration was 18 weeks (range 3-115) and 33 patients remain on treatment with raludotatug deruxtecan.

Summary of Ovarian Cancer Subset Efficacy Analysis of Phase 1 Trial

Efficacy Measure

Patients with ovarian cancer receiving doses of

raludotatug deruxtecan (between 4.8 and 8.0 mg/kg), evaluable for RECIST v.1.1

n=50

Confirmed ORR, % (95% CI)

46% (32–61)

CR, n

1

PR, n

22

DCR

98%

DOR, median (95% CI), months

11.2 months (3.0-NE)

PFS, median (95% CI), months

7.9 months (4.4-12.4)

CR, complete response; DCR, disease control rate; DOR, duration of response; ORR, objective response rate; PR, partial response; PFS, progression-free survival.

About the Phase 1 Trial
The phase 1 trial is the first-in-human, open-label study evaluating the safety and efficacy of raludotatug deruxtecan in patients with advanced ovarian cancer resistant or refractory to standard of care and previously treated with platinum-based and taxane chemotherapy. Patients were not selected based on tumor CDH6 expression status.

The first part of the trial (dose escalation) assessed the safety and tolerability of increasing doses of raludotatug deruxtecan to determine the maximum tolerated dose and/or recommended dose for expansion (RDE) in patients with advanced ovarian tumors. The second part of the trial (dose expansion) initially evaluated the safety and efficacy of raludotatug deruxtecan at the RDE of 8.0 mg/kg, which was discontinued as of October 2022. Further assessment is currently ongoing at the 4.8, 5.6 and 6.4 mg/kg doses.

The trial will evaluate safety endpoints including dose-limiting toxicities and adverse events as well as efficacy endpoints including ORR by investigator assessment, DOR, DCR, time to response and PFS. Pharmacokinetic and exploratory biomarker endpoints also will be assessed.

Patient enrollment in the dose expansion part of the trial remains underway in Asia and North America. For more information, please visit ClinicalTrials.gov.

About Ovarian Cancer
Approximately 314,000 women were diagnosed with ovarian cancer worldwide in 2020 and more than 207,000 died from the disease.4,5 Approximately 70% to 80% of patients diagnosed with ovarian cancer will have a recurrence of disease following standard treatment with platinum-based chemotherapy regimens.1 For patients that develop resistance to platinum-based chemotherapy, treatment options are limited.6

The introduction of targeted treatments has increased treatment options and improved survival outcomes for some patients with ovarian cancer, but new therapeutic approaches are needed for tumors that progress on available medicines.7

About CDH6
CDH6 (human cadherin-6) is a cadherin family protein overexpressed in several cancers, particularly ovarian tumors.2 An estimated 65% to 85% of patients with ovarian cancer have expression of CDH6, which is associated with poor prognosis.2,3 No CDH6 directed cancer therapies are currently approved for treatment of any cancer.

On October 22, 2023 Agenus Inc. (Nasdaq: AGEN), a leader in developing novel immunological agents to treat cancers, reported first-time and updated data from its ongoing botensilimab/balstilimab (BOT/BAL) clinical programs in advanced colorectal cancer (CRC), neoadjuvant CRC, pancreatic cancer, non-small cell lung cancer (NSCLC), melanoma, and sarcoma (Press release, Agenus, OCT 22, 2023, View Source [SID1234636230]). Members of the Agenus leadership team along with key opinion leaders will discuss these findings during a live webcast at 1:00 p.m. EDT (19:00 CEST) at a corporate event at the European Society for Medical Oncology 2023 Conference.

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"BOT’s versatility, alone, in combination with BAL, or in combination with other standard of care therapies, in early and late-stage solid tumors, positions Agenus to transform cancer care, offering immense promise to patients."

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"These new and updated data underscore BOT’s broad effectiveness across several advanced solid tumors, demonstrating its potential beyond first-generation immunotherapies and current treatments," said Dr. Steven O’Day, Chief Medical Officer. "BOT’s versatility, alone, in combination with BAL, or in combination with other standard of care therapies, in early and late-stage solid tumors, positions Agenus to transform cancer care, offering immense promise to patients."

Key highlights across solid tumors include:

Extended Follow-up and Additional Data in Refractory MSS CRC Demonstrate Improved Responses and Durability

In 70 efficacy evaluable patients with MSS CRC and no active liver metastases:

Confirmed (RECIST 1.1) overall response rate (ORR) of 24% was observed, compared to 2.8% reported with standard of care (SOC) in 2/3L+ MSS CRC patients with no active liver metastases1.
12-month overall survival (OS) of 74% and median OS (mOS) not yet reached. Median follow up now 12.3 months.
Subsequent data from expanded cohorts and early signals from a 230 patient Phase 2 trial is consistent with the earlier cohort of 70 patients. Based on the totality of the evidence from the Phase 1 and Phase 2 trials, Agenus plans to submit its Biologics License Application (BLA) to the U.S. Food & Drug Administration (FDA) for BOT/BAL in patients with 2/3L+ MSS CRC in midyear 2024. Interactions with U.S. and EU regulatory agencies are ongoing.

Robust Clinical Outcomes in Neoadjuvant MSS CRC Underscore BOT/BAL’s Potential in Earlier-Stage Patients*

All patients treated with one dose of BOT and two doses of BAL.
After dosing, observations of responses were made within approximately four-weeks prior to surgery.
100% (3/3) of patients with MSI-H CRC had major pathological responses (>90%).
67% (6/9) patients with MSS CRC had pathological responses of >50%, which includes two complete pathological responses.
These findings offer an alternative path to minimize or eliminate radical rectal surgery and its associated morbidities such as colostomy dependance and sexual dysfunction, and potentially avoid the need for systemic chemotherapy.
Agenus plans to prioritize neoadjuvant development and is evaluating study design for further regulatory activity.
Compelling Activity from Dose-escalation Portion of Phase 2 BOT/Chemotherapy Combination in Advanced (2L) Pancreatic Cancer

In FOLFIRINOX relapsed/refractory (2L) pancreatic cancer, 80% of evaluable patients (n=5; 150mg BOT+gem-Abraxane) experienced sustained tumor marker reductions. All patients had liver metastases.
Two partial responses were at 16 weeks with target lesion reduction of -47% (confirmed) and -37% (pending confirmation), and both responses remain ongoing.
Two other patients showed stable disease with tumor reduction of -20% and -13% at 8 weeks and remain on study awaiting 16-week scans.
A Phase 2 randomized study is enrolling.
Monotherapy Activity in CTLA-4 Relapsed/Refractory Advanced (2L+) Melanoma

Phase 1 expansion cohort in relapsed/refractory (2L+) melanoma (n=10) showed a 30% ORR and 60% disease control rate; 8/10 patients had multiple prior lines including anti-PD-1/CTLA-4 and failed BRAF targeted therapy (n=5).
An accelerated Phase 2 trial in patients who have failed anti-CTLA-4 and PD-1 is underway; BOT monotherapy cohort is fully enrolled and BOT/BAL combination is enrolling.
Compelling Responses in Refractory NSCLC

Patients treated with PD(L)-1 refractory NSCLC were treated with BOT/BAL combination and showed a 56% ORR and 89% disease control rate (n=9).
Importantly, in patients with EGFR mutations refractory to SOC responded to the BOT/BAL combo, with one patient experiencing an -90% tumor reduction** at 12 weeks and the second having a -42% tumor reduction at 6 weeks and is pending confirmation.
Expansion cohorts are underway with anticipated enrollment of 100 patients by 1Q 2024.
Additional data from this study will be reported in midyear 2024.
Broad and Durable Activity in Advanced Sarcomas

Updated data was presented at ESMO (Free ESMO Whitepaper) 2023 from the Phase 1b study in 41 efficacy evaluable heavily pretreated advanced sarcoma patients, demonstrating durability with extended follow-up and additional activity in difficult-to-treat subtypes such as leiomyosarcoma.

BOT/BAL combination demonstrated 6-month progression-free survival of 40%, ORR of 20%, and median response duration of 19.4 months (iRECIST).
Differential responses observed by dose level, with 29% ORR at 2 mg/kg BOT compared to 15% at 1 mg/kg BOT.
Webcast Details

A live webcast will be held today at 19:00 – 21:00 CEST (1:00 p.m. – 3:00 p.m. EDT). To register for the webcast, please click here.

References:

Cohen et al. "Prognostic value of liver metastases in colorectal cancer treated by systemic therapy: An ARCAD pooled analysis." ASCO (Free ASCO Whitepaper) Annual Meeting 2023, Abstract 3554
*Investigator Sponsored Trial
**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 750 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.