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Artios Presents Positive Initial Phase 1/1b Clinical Monotherapy Data for ATR Inhibitor ART0380 in Advanced Solid Tumors at the European Society of Medical Oncology Congress 2023

On October 23, 2023 Artios Pharma Limited (Artios), a clinical-stage biotech company led by pioneers of DNA damage response ("DDR") drug development, reported promising monotherapy data from the Phase 1/1b portion of the ongoing Phase 1/2a study (NCT04657068) of its ataxia telangiectasia and Rad-3 related ("ATR") kinase inhibitor ART0380 in advanced or metastatic solid tumors as part of a poster presentation at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (ESMO) (Free ESMO Whitepaper) 2023 (Press release, Artios Pharma, OCT 23, 2023, View Source [SID1234636236]). ART0380 is a clinically advanced, oral, highly potent, and selective ATR inhibitor with best-in-class potential. The Phase 1/1b portion of the trial presented at ESMO (Free ESMO Whitepaper) assessed the safety and tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of ART0380 monotherapy in patients with advanced or metastatic solid tumors. The patient population was enriched for cancers harboring DNA damage response deficiencies as identified by the Artios DcoDeR platform (n = 49).

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Dr. Niall Martin, Chief Executive Officer at Artios, said: "As a master regulator of replication stress, ATR inhibition can increase DNA damage and powerfully suppress tumor growth across broad cancer types harboring genetic defects. However, durability and long-term use with first-generation ATR inhibitors has been limited by challenges with toxicity and tolerability. Our next-generation ATR inhibitor ART0380 has demonstrated highly encouraging molecular and clinical responses as a monotherapy particularly in patients with DDR deficiency and high replication stress alterations. We believe the predictable and manageable safety profile and reliable pharmacokinetics of ART0380 offers combination flexibility as well as continuous and intermittent dosing regimen options. We look forward to further evaluating the therapeutic potential of ART0380 alone and in combination with chemotherapies in patients with selected cancer biologies as part of the ongoing Phase 2 trial. We expect initial Phase 2 combination data with gemcitabine in patients with platinum resistant ovarian cancer in the first half of 2025, and with irinotecan in ATM deficient cancers in the second half of 2024."

Key Phase 1/1b efficacy data support ART0380 is active across tumor types:

Molecular responses and reduction in tumor size observed in multiple cancer types, including those harboring molecular alterations or biology consistent with high replication stress
Molecular responses were associated with longer progression free survival (PFS)
Durable confirmed responses in all enrolled patients with high grade endometrial cancer
Potent tumor-specific DNA damage detected by selective increases in γH2Ax in circulating tumor cells but not normal cells in DDR deficient tumors predicted through Artios’ DcoDeR platform
Key Phase 1/1b safety and PK data demonstrate ART0380 is well-tolerated and predictable:

Safe and well tolerated at intermittent and continuous doses
Predictable, manageable, and reversible on-target anemia
Dose proportional increases in exposure with rapid absorption and relatively rapid elimination and low variability
The global, open-label, multi-center, Phase 1/2a study is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of ART0380 as a monotherapy or in combination with gemcitabine or irinotecan in patients with advanced or metastatic solid cancers. In the Phase 1/1b portion of the trial, patients with advanced solid cancers receiving escalating doses of ART0380 on a continuous daily (QD) or intermittent (3 days on, 4 days off) schedule will be evaluated. Patient enrollment was enriched for those with cancers harboring DNA damage response deficiencies as identified by the Artios DcoDeR platform. The Phase 2 portion will evaluate intermittent dosing of ART0380 in combination with gemcitabine in patients with platinum-resistant high grade serious ovarian, primary peritoneal or fallopian tube carcinoma, and in combination with irinotecan in ATM deficient cancers. Up to 250 patients are expected to be enrolled in the Phase 1/2a study which will be conducted at multiple oncology centers across the United States and Europe.

ART0380 is being developed as an oral anti-cancer agent for the treatment of cancers that harbor defects in DNA repair and in combination with agents including those that cause DNA damage. ART0380 was originally in-licensed by Artios from The University of Texas MD Anderson Cancer Center and ShangPharma Innovation in 2019. The molecule was jointly developed as part of a collaboration between ShangPharma and MD Anderson’s Therapeutics Discovery Division.

Aptose to Hold Clinical Update and KOL Data Review of AML Drug Tuspetinib on Monday, October 30th

On October 23, 2023 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated oral kinase inhibitors to treat hematologic malignancies, reported that the Company will provide a clinical update on Monday, October 30, 2023 at 8:30 AM Eastern Time, in conjunction with poster presentations at the European School of Haematology (ESH) 6th International Conference: Acute Myeloid Leukemia "Molecular and Translational": Advances in Biology and Treatment, being held October 29-31, 2023, in Estoril, Portugal (Press release, Aptose Biosciences, OCT 23, 2023, View Source [SID1234636235]).

The webcast event will include a comprehensive review of up-to-date clinical data for Aptose’s lead compound tuspetinib and will feature Naval Daver, MD, Professor, Director Leukemia Research Alliance Program, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX. Dr. Daver is the lead investigator on Aptose’s APTIVATE trial and is recognized for significant achievements in the development of novel AML treatments, including several combination therapies.

Tuspetinib (TUS), a once-daily oral tablet, is a precision targeted myeloid kinase inhibitor that suppresses a select handful of kinases known to drive the proliferation of acute myeloid leukemia (AML) but avoids other kinases that can compromise safety. Tuspetinib as a single agent was well-tolerated and highly active among relapsed or refractory (R/R) AML patients with a diversity of adverse genotypes and delivered a 42% CR/CRh across evaluable venetoclax (VEN) naïve patients at the 80mg daily RP2D. Tuspetinib also is being studied in combination with venetoclax (VEN) in the APTIVATE international Phase 1/2 expansion trial in R/R AML patients. The TUS/VEN doublet has been well tolerated and achieved multiple responses in patients who previously failed venetoclax (Prior-VEN failure AML), including Prior-VEN failure patients who also previously failed FLT3 inhibitors, all of whom represent emerging populations of high unmet medical need. Notably, tuspetinib targets venetoclax resistance mechanisms that may re-sensitize Prior-VEN failure patients to venetoclax.

Aptose Clinical Update Details

Date & Time: Monday, October 30, 2023, 8:30 AM ET

Participant Webcast Link: here (View Source)

The slides will be available on Aptose’s website here and the webcast of the presentation will be archived shortly after the conclusion of the event.

Poster Presentations

As announced prior, the Aptose poster presentations at ESH are listed below. Note that the poster presentations will include additional data not found in the abstracts. The posters accepted for presentation are listed below and can be viewed beginning October 29, 2023, on site at the ESH poster exhibit hall and online on the Aptose website here.

Tuspetinib Myeloid Kinase Inhibitor Safety and Efficacy as Monotherapy and Combined with Venetoclax in Phase 1/2 Trial of Patients with Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML)

Tuspetinib Oral Myeloid Kinase Inhibitor Creates Synthetic Lethal Vulnerability to Venetoclax

Aligos Therapeutics Announces $92 Million Private Placement Financing

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]).

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.

Immutep’s Efti in Combination with KEYTRUDA® Generates Excellent Overall Survival Benefit in Patients with Metastatic Non-Small Cell Lung Cancer

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]).

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).

Analysis from TRACERx Study Reveals More Sensitive and Earlier ctDNA Detection in Lung Cancer Patients by Personalis’ MRD Technology

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.

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.