On May 23, 2024 Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through the development of best-in-class IL-2 therapeutics, reported interim results from its Phase 1/2 trial of AU-007, the first human monoclonal antibody designed using artificial intelligence to be tested in a clinical trial (Press release, Aulos Bioscience, MAY 23, 2024, View Source [SID1234643620]). The data will be presented in a poster session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2024 Annual Meeting in Chicago, Illinois.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The level and scope of anti-tumor activity we’re seeing across solid tumor types are remarkable so early in clinical development, particularly the partial responses and metabolic complete response. The durability of the tumor reductions seen in several patients suggests the formation of immune memory of the cancerous cells. These results validate our long-held belief that AU-007 could widen the therapeutic window of IL-2 by redirecting IL-2 toward CD8+ T and natural killer cells that can kill tumor cells and away from immunosuppressive regulatory T cells and the vasculature," said Aron Knickerbocker, Aulos Bioscience’s chief executive officer. "While other developmental IL-2 therapies focus on changing IL-2 itself, AU-007 is a human antibody that is a well-established therapeutic modality. This provides sources of advantage and differentiation. As we treat patients in earlier lines of therapy, we are confident AU-007 is emerging as a potential best-in-class regimen."

Key findings from the updated results of the AU-007 Phase 1/ 2 study, with data available on 59 patients as of the data cutoff date of April 9, 2024, are as follows.

Well-tolerated safety profile:

No evidence of vascular leak syndrome or pulmonary edema reported at all dose levels evaluated.
All drug-related adverse events were Grade 1 or 2 except for:
One patient with Grade 4 CRS that resolved quickly with steroids. This patient was noted retrospectively to have subclinical elevated IL-6 serum levels at baseline.
Five patients experienced transient (3-7 days) Grade 3 or 4 lymphopenias that were not associated with adverse outcomes. Transient lymphopenia is a known effect of IL-2 treatment as lymphocytes traffic out of blood and into tissue.
One patient with Grade 3 anemia who entered the study with Grade 2 anemia.
Profound and durable tumor shrinkage observed in multiple tumor types:

A patient with large-volume metastatic melanoma whose tumors had progressed through anti-PD-1 and anti-CTLA-4 checkpoint inhibitors was treated with AU-007 (9 mg/kg) and one 135K IU/kg low dose of IL-2 and experienced 76% shrinkage (unconfirmed partial response) in target lesions at 8 weeks.
Another patient with metastatic melanoma whose tumors had also progressed through anti-PD-1 and anti-CTLA-4 checkpoint inhibitors was treated with AU-007 (4.5 mg/kg) and one 15K IU/kg low dose of IL-2 and achieved 48% shrinkage in target lesions.
A patient with head and neck cancer whose tumors had progressed through an anti-PD-1 checkpoint inhibitor was treated with AU-007 (4.5 mg/kg) and 45K IU/kg IL-2 dose every two weeks and experienced 32% shrinkage (confirmed partial response) in a cervical bone metastasis, as well as reduced pain and improved motor function in an affected hand.
A patient with bladder cancer whose tumors had progressed through an anti-PD-L1 checkpoint inhibitor was treated with AU-007 (4.5 mg/kg) and one 45K IU/kg IL-2 dose and achieved a durable metabolic complete response.
Additional tumor shrinkages were observed in patients with widespread large-volume disease in renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC) and MSI-stable (MSS) colorectal cancer.
Unique pharmacodynamic (PD) and pharmacokinetic (PK) profiles in the IL-2 class:

Decreases in peripheral regulatory T cells (Tregs) and increases in CD8/Treg ratios demonstrate AU-007’s ability to redirect IL-2 and prevent the negative feedback loop to Tregs. AU-007 and low-dose aldesleukin also substantially increases peripheral natural killer (NK) cells.
AU-007 PK demonstrates dose-proportionality over the dose range tested and no signs of neutralizing anti-drug antibodies (ADAs) activity, and a half life of 15+ days.
The Phase 2 expansion cohorts of the AU-007 study are continuing to enroll patients with a focus on melanoma and RCC. The company anticipates presenting updated clinical data in the second half of 2024. Additional Phase 2 expansion cohorts are planned to evaluate AU-007 and aldesleukin in second-line PD-L1+ NSCLC, with and without the PD-L1 antibody avelumab.

The poster, "Updated results of a phase 1/2 study of AU-007, a monoclonal antibody (mAb) that binds to IL-2 and inhibits CD25 binding, in patients with advanced solid tumors," (Abstract 2527) is available to meeting registrants as an electronic poster on the ASCO (Free ASCO Whitepaper) online meeting platform and will be presented live in the poster session "Developmental Therapeutics—Immunotherapy" on Saturday, June 1, 2024, 9:00 a.m. to 12:00 p.m. CDT.

To learn more about the AU-007 clinical trial program, please visit ClinicalTrials.gov (identifier: NCT05267626). For patients and providers in the U.S., please visit www.solidtumorstudy.com. For patients and health professionals in Australia, please visit www.solidtumourstudy.com.

About AU-007
AU-007 is a human IgG1 monoclonal antibody designed using artificial intelligence that is highly selective to the CD25-binding portion of IL-2. With a mechanism of action unlike any other IL-2 therapeutic in development, AU-007 leverages IL-2 to reinforce anti-tumor immune effects. This is achieved by preventing IL-2, either exogenous or secreted by effector T cells, from binding to trimeric receptors on regulatory T cells while still allowing IL-2 to bind and expand effector T cells and NK cells. This prevents the negative feedback loop caused by other IL-2-based treatments and biases the immune system toward activation over suppression. AU-007 also prevents IL-2 from binding to CD25-containing receptors on eosinophils, as well as vasculature and pulmonary endothelium, which may significantly reduce the vascular leak syndrome and pulmonary edema associated with high-dose IL-2 therapy.

On May 23, 2024 Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported that an update from the Company’s AFM24-102 study in advanced EGFR wild-type (EGFRwt) non-small cell lung cancer (NSCLC) will be presented at the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) to be held in Chicago on May 31 – June 4, 2024 (Press release, Affimed, MAY 23, 2024, View Source [SID1234643619]). Patients in the study are treated with the combination of AFM24, Affimed’s innate cell engager (ICE), and atezolizumab, Roche’s checkpoint inhibitor (CPI).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

As of the March 18 cut-off for the poster, 17 patients with EGFRwt NSCLC received the combination treatment and 15 patients were response evaluable. One patient showed a confirmed complete response, and three patients showed confirmed partial responses (PR). In addition, seven patients achieved stable disease, resulting in a disease control rate of 73.3% (11/15 patients). Median progression-free survival was 5.9 months.

All responders were resistant to checkpoint inhibitor treatment prior to the study, which supports the hypothesis that combining AFM24 with atezolizumab may enhance the cancer-immunity cycle and provide an alternative strategy to overcome resistance to existing therapies for EGFR-expressing tumors.

AFM24 and atezolizumab were given at their respective single agent doses. Treatment in these heavily pretreated patients was well tolerated. Side effects were consistent with the known safety profiles of these agents. The most frequent side effects observed were mild to moderate infusion related reactions and transient mild to moderate increase in liver enzymes.

"We are very encouraged to see objective and lasting responses in patients who have failed multiple lines of therapy including platinum doublets and checkpoint inhibitors," said Dr. Andreas Harstrick, Chief Medical and acting Chief Executive Officer of Affimed. "These data support our hypothesis that the combination of AFM24 and PD-1 targeting may act synergistically on the immunity cycle. It is remarkable that this can be achieved with a chemotherapy-free approach. We are committed to continuing clinical development of this therapy and are enrolling additional patients for both EGFRwt and EGFRmut NSCLC."

The EGFRwt NSCLC cohort of the study will enroll up to 40 patients and the EGFRmut NSCLC cohort will enroll up to 25 patients.

The full data set will be presented by Dr. Hye Ryun Kim, Professor at Yonsei University College of Medicine, Seoul, Korea, at ASCO (Free ASCO Whitepaper) on June 1, 2024, during the poster session on Developmental Therapeutics—Immunotherapy (9:00 a.m.—12:00 p.m. CDT).

The abstract and more details about the ASCO (Free ASCO Whitepaper) conference are available online at Attend | ASCO (Free ASCO Whitepaper) Annual Meeting. The poster will be available online at View Source the presentation.

Conference Call and Webcast Information

Affimed will host a conference call and webcast for the financial community on June 1, 2024, at 6:00 p.m. CDT / 7:00 p.m. EDT.

The conference call will be available via phone and webcast. The live audio webcast of the call will be available in the "Webcasts" section on the "Investors" page of the Affimed website at View Source To access the call by phone, please use link:

https://register.vevent.com/register/BIff607338e5d247f99b548240be2ad413, and you will be provided with dial-in details and a pin number.

About AFM24

AFM24 is a tetravalent, bispecific ICE that activates the innate immune system by binding to CD16A on innate immune cells and epidermal growth factor receptors (EGFR), a protein widely expressed on solid tumors, to kill cancer cells. Generated by Affimed’s fit-for-purpose ROCK platform, AFM24 represents a distinctive mechanism of action that uses EGFR as a docking site to engage innate immune cells for tumor cell killing through antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.

On May 23, 2024 Theratechnologies Inc. ("Theratechnologies" or the "Company") (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies, reported Phase 1 data demonstrating signs of long-term efficacy and a manageable safety profile of its lead investigational peptide drug conjugate (PDC) candidate, sudocetaxel zendusortide (TH1902), in patients with solid tumors (Press release, Theratechnologies, MAY 23, 2024, View Source [SID1234643618]). The data will be presented in a poster session on June 1, 9:00 AM-12:00 PM CDT (abstract #3081, poster board #226) at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, which is taking place May 31-June 4, 2024, in Chicago, IL.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In an updated analysis from Parts 1 and 2 of an ongoing Phase 1 clinical trial, sudocetaxel zendusortide induced durable disease stabilization (up to 45 weeks) lasting beyond treatment completion. The results suggest a unique, multimodal mechanism of action distinct from other cancer therapeutics, including induction of immune cell infiltration even in "cold" tumor models, inhibition of vasculogenic mimicry, targeting of chemotherapy-resistant cancer stem cells, and activation of the cGAS/STING immune pathway, among other actions. Additionally, investigators observed an early efficacy signal primarily in female cancers (ovarian cancer, endometrial cancer, triple-negative breast cancer [TNBC]), with seven of 16 participants (44%) achieving a clinical benefit rate (complete response + partial response + stable disease), as confirmed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The poster presentation, which constitutes the first report of long-term efficacy, safety, and pharmacokinetic (PK) data from the Phase 1 study, also suggests that sudocetaxel zendusortide has a manageable safety profile when dosed at 300mg/m2, with few Grade 3 adverse events (AEs).

"The initial long-term Phase 1 data further validate and expand upon the preliminary evidence of antitumor activity with sudocetaxel zendusortide in individuals with solid tumors," said Ira Winer, M.D., Ph.D., FACOG, a member of the Gynecologic Oncology and Phase 1 Clinical Trials Multidisciplinary Teams at Karmanos Cancer Center and Associate Professor of Oncology at Wayne State University. "It is highly unusual to see such long-lasting disease stabilization even after treatment cessation in patients with advanced disease. These updated data provide an informative baseline as we seek to optimize the dose of this novel peptide-drug conjugate in patients with platinum-resistant ovarian cancer in the next stage of the Phase 1 trial."

Study details

Dr. Winer and colleagues conducted an analysis of the long-term efficacy, safety, and PK of sudocetaxel zendusortide from Parts 1 and 2 of the Phase 1 trial, which seeks primarily to characterize the agent’s safety and tolerability. Part 1 (modified intrapatient dose escalation, n=18) included patients with recurrent/refractory advanced tumors (all comers) with no limit on the number of previous therapies, including taxanes. Part 2 (dose expansion, n=18) included patients with cancers with known high expression of the sortilin (SORT1) receptor, including ovarian cancer, endometrial cancer, TNBC, and melanoma. Part 3 (dose optimization) of the Phase 1 trial, in patients with advanced ovarian cancer that is no longer platinum-sensitive, is ongoing.

In a sub-analysis of efficacy in 16 patients with TNBC, ovarian, and endometrial cancers, seven patients exhibited RECIST 1.1-confirmed clinical benefit, with six patients achieving long-term stabilization of disease (up to a maximum of 45 weeks in duration) even after drug discontinuation in some patients. One patient with ovarian cancer had an overall partial response (PR), with a RECIST 1.1-confirmed complete response (CR) in target lesions, and stabilization of disease (SD) in non- target lesions, lasting up to 24 weeks from initiation of treatment. In addition, one patient with endometrial cancer, whose dose was escalated from 60 mg/m2 to 360 mg/m2 in Part 1, completed a total of 11 treatment cycles; this patient’s disease remained stable throughout eight months of treatment, up to the time of consent withdrawal. All 16 patients had prior exposure to taxane-containing regimens (range: 1-6). The investigators characterized the prolonged stabilization of disease as clinically significant in this heavily pretreated patient population, which typically experiences recurrence during or shortly after treatment discontinuation.

Sudocetaxel zendusortide has a manageable safety profile, with most treatment-related AEs rated as mild to moderate in severity and managed with standard supportive care or dose reductions. Investigators noted that the low number of Grade 3 AEs compares favorably to the published literature for unconjugated docetaxel.

PK measures showed that exposure to free docetaxel was much lower than that for sudocetaxel zendusortide, a finding that may explain the lower incidence and severity of AEs seen with sudocetaxel zendusortide versus docetaxel alone. The maximum concentration (Cmax) of sudocetaxel zendusortide was 30.4 micromolar (μM), compared to 0.58 μM for free docetaxel. The 24-hour area under the curve (AUC24) for sudocetaxel zendusortide was 74.8 nanomoles per hour per liter (h.nmol/mL), versus 3.1 h.nmol/mL for free docetaxel. The free docetaxel/sudocetaxel zendusortide AUC ratio was less than 1% up to 300 mg/m2, suggesting that most docetaxel remains associated with the peptide over the period of analysis.

"One year after our presentation of preliminary evidence of antitumor activity at the 2023 ASCO (Free ASCO Whitepaper) annual meeting, the Phase 1 sudocetaxel zendusortide trial continues to yield important information about long-term efficacy, safety, and pharmacokinetics of this promising peptide-drug conjugate," commented Christian Marsolais, Ph.D., Senior Vice President and Chief Medical Officer at Theratechnologies. "These latest data leave us well positioned for Part 3 of the study, in which we aim to optimize the dose to see further signs of efficacy while limiting toxicity. We look forward to sharing more data from this ongoing trial in the future."

About Sudocetaxel Zendusortide (TH1902) and SORT1+ Technology

Sudocetaxel zendusortide is a first-of-its-kind sortilin receptor (SORT1)-targeting PDC, and the first compound to emerge from the Company’s broader licensed oncology platform. A new chemical entity, sudocetaxel zendusortide employs a cleavable linker to conjugate (attach) a proprietary peptide to docetaxel, a well-established cytotoxic chemotherapeutic agent used to treat many cancers. The FDA granted Fast Track designation to sudocetaxel zendusortide as a single agent for the treatment of all sortilin-positive recurrent advanced solid tumors that are refractory to standard therapy. Sudocetaxel zendusortide is currently being evaluated in a Phase 1 clinical trial.

Theratechnologies has established the SORT1+ Technology platform as an engine for the development of PDCs that target SORT1, which is expressed in multiple tumor types. SORT1 is a "scavenger" receptor that plays a significant role in protein internalization, sorting, and trafficking. Expression of SORT1 is associated with aggressive disease, poor prognosis, and decreased survival. It is estimated that SORT1 is expressed in 40% to 90% of endometrial, ovarian, colorectal, triple-negative breast (TNBC), and pancreatic cancers, making this receptor an attractive target for anticancer drug development.

On May 23, 2024 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), a clinical stage immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients, reported encouraging clinical data from the dose escalation portion of its Phase 1/2 trial of SNS-101, a conditionally active, human monoclonal antibody targeting the immune checkpoint VISTA (V-domain Ig suppressor of T cell activation) (Press release, Sensei Biotherapeutics, MAY 23, 2024, View Source [SID1234643617]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"I am pleased that SNS-101 has been well-tolerated in the study, reaching its highest planned dose level with no dose limiting toxicities and demonstrating its potential to successfully overcome the prior challenges of VISTA-targeted programs," said Dr. Shiraj Sen, Medical Oncologist and Director of Clinical Research at NEXT Oncology, Dallas, and a principal investigator for the SNS-101 study. "The data show encouraging signs of clinical activity in a heterogeneous population of patients with advanced solid tumors, where you typically wouldn’t expect to see clinical responses, especially in microsatellite stable colorectal and endometrial tumors. There is a continued unmet need for patient populations that have become resistant or don’t respond to current immunotherapy treatment options. I look forward to continuing to evaluate its progress."

Dose escalation portion of the Phase 1/2 clinical trial

The dose escalation portion of the Phase 1/2 clinical trial is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of SNS-101. This study assesses SNS-101 both as monotherapy and in combination with Regeneron’s PD-1 inhibitor Libtayo (cemiplimab, 350 mg), in patients with advanced solid tumors with primary (unfavorable candidates for immunotherapy) or acquired PD-1 therapy resistance (progressed on prior anti-PD-1 therapy).

A total of 34 patients received SNS-101 once every 3 weeks, with 16 patients in the monotherapy arm and 18 patients in the combination arm. The majority of patients (85%) had a tumor type that is typically unresponsive to PD-1 monotherapy ("cold" tumors).

As of the April 30, 2024 data cutoff, SNS-101 demonstrated preliminary evidence of promising clinical activity in multiple tumor types, including:

One microsatellite stable (MSS) endometrial cancer patient that received SNS-101 plus cemiplimab had a confirmed partial response (59% decrease) and remains on study at 30+ weeks. MSS endometrial cancer has been previously shown to have a low response rate to monotherapy immunotherapy treatments.
One MSS colorectal cancer (CRC) patient that received SNS-101 plus cemiplimab remained on study for 18 weeks and had tumor regression of 27%. MSS CRC has been previously shown to be unresponsive to PD-1 treatments.
One pembrolizumab-resistant renal cell carcinoma patient that received SNS-101 plus cemiplimab remained on study for 12 weeks and had tumor regression of 18%.
One pembrolizumab-resistant human papillomavirus (HPV)+ head and neck cancer patient that received SNS-101 as monotherapy remained on study for 12 weeks and had tumor regression of 17%.
These clinical data are consistent with preclinical studies suggesting therapeutically relevant clinical doses of SNS-101 at 3mg/kg or higher. Additionally, preliminary flow-based pharmacodynamic analysis showed dose-dependent changes in specific T-cell populations suggesting SNS-101 may be having a pharmacological effect on T-cell subsets.

SNS-101 demonstrated a potentially best-in-class pharmacokinetic (PK) profile with linear elimination kinetics and dose-proportional increases in exposure, supporting once every three week dosing. The data are consistent with lack of target-mediated drug disposition (TMDD), which has been observed in non-conditionally active anti-VISTA antibodies.

SNS-101 was well tolerated alone and in combination with cemiplimab, with no dose-limiting toxicities observed. The majority of AEs were Grade 1 or 2 in severity. Two patients experienced Grade 1 cytokine release syndrome (CRS), one in monotherapy and one in combination, both at the highest dose of SNS-101. Both cases were mild and manageable, demonstrating that SNS-101 has the potential to overcome a key hurdle that hindered first-generation VISTA-targeting approaches. Four patients in the combination cohort experienced immune-mediated events. There were also no significant changes to key inflammatory cytokine levels, including interferon gamma, interleukin-6, interleukin-10, interleukin-8, TNF-alpha, and CCL5-RANTES, across cohorts.

"The dose escalation portion of the Phase 1/2 trial of SNS-101 answers the critical question of whether a pH-selective approach can overcome the previous hurdles associated with targeting VISTA, which included severe safety and PK issues. We believe the topline data presented today marks an important milestone and validates the mechanism of action by demonstrating the potentially best-in-class PK and a well-tolerated safety profile of SNS-101 at therapeutically relevant dose levels," said Ron Weitzman, Chief Medical Officer of Sensei Bio. "We saw promising clinical activity primarily in tumor types that don’t typically respond to PD-1 monotherapy and look forward to progressing through the expansion phase of the study."

Ongoing dose expansion portion of the Phase 1/2 clinical trial

Patient enrollment is advancing in the dose expansion portion of the Phase 1/2 study. The Company expects to report initial data from the dose expansion cohorts and to hold an end-of-Phase 1 meeting with the FDA by the end of 2024.

ASCO presentation

The data will be presented in a poster presentation entitled "Initial results from a first-in-human phase 1 study of SNS-101 (pH-selective anti-VISTA antibody) alone or in combination with cemiplimab in patients with advanced solid tumors," on June 1, 2024, at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held in Chicago, IL. The poster will be available on the Sensei website at the start of the poster presentation.

Investor webcast

Sensei will host a webcast on Monday, June 3, 2024, at 8:00 a.m. ET (7:00 a.m. CT) to discuss the data. Participating alongside Company management will be Dr. Shiraj Sen, M.D., Ph.D., Medical Oncologist and Director of Clinical Research at NEXT Oncology-Dallas. Dr. Sen is an investigator on the ongoing Phase 1/2 clinical trial for SNS-101, and lead author of the SNS-101 poster. The live event can be accessed here: View Source and can be accessed on the Investor page of Sensei’s website at View Source A replay of the webcast will be available after the completion of the event.

On May 23, 2024 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) reported upcoming presentations from their commercial and clinical-stage hematology and oncology portfolio at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Hybrid Congress (Press release, Rigel, MAY 23, 2024, View Source [SID1234643616]). The ASCO (Free ASCO Whitepaper) Annual Meeting is being held online and in person in Chicago, Illinois from May 31 to June 4, 2024. The EHA (Free EHA Whitepaper)2024 Congress is being held online and in person in Madrid, Spain from June 13 to June 16, 2024.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Rigel’s presentations will include data for REZLIDHIA (olutasidenib), for the treatment of mutated isocitrate dehydrogenase-1 (mIDH1) acute myeloid leukemia (AML), and TAVALISSE (fostamatinib), for the treatment of chronic immune thrombocytopenia (ITP), along with an overview of the ongoing Phase 1b trial evaluating R2891, a potent and selective inhibitor of IRAK1 and IRAK4, in patients with lower-risk myelodysplastic syndrome (LR-MDS) who are refractory or resistant to prior therapies.

"We are excited to present new data on REZLIDHIA that adds to the growing body of evidence supporting its efficacy and safety in patients with mIDH1 AML, including difficult to treat patient populations. The five-year data from the registrational Phase 2 trial continue to demonstrate that REZLIDHIA induces rapid and durable responses. In addition, new analyses support the benefit it may provide to elderly patients," said Raul Rodriguez, Rigel’s president and CEO. "The collective data to be presented at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) underscore the strength and compelling science of our hematology and oncology portfolio."

Highlights from the robust REZLIDHIA (olutasidenib) data published include:

An additional two years of data, beyond the results that led to FDA approval of olutasidenib, further demonstrates the durable responses observed with olutasidenib in heavily pretreated patients with mIDH1 AML, including those relapsed or refractory (R/R) to prior venetoclax. The safety profile was consistent with what was previously reported.
Olutasidenib was generally well tolerated in elderly patients with R/R mIDH1 AML and induced durable remissions. Despite the challenges of treating elderly patients who had already failed prior AML treatment, the results suggest that elderly patients can benefit from therapy with olutasidenib.
Olutasidenib was effective in achieving remission in patients with mIDH1 R/R AML and served as a bridging strategy towards potentially curative allogeneic transplantation in a substantial subset of these previously ineligible patients.
Olutasidenib was well tolerated in a subset of patients with post-myeloproliferative neoplasms (MPN) mlDH1 AML, a patient population often associated with poor responses to available therapies.
Data from the TAVALISSE (fostamatinib) observational study provides greater insight into use in the real-world setting:

In the study, fostamatinib demonstrated efficacy and safety as second-line therapy for ITP. Fostamatinib allowed successful tapering and discontinuation of corticosteroids while maintaining platelet counts above 50,000/μL.
ASCO Annual Meeting abstracts may be accessed online via View Source Details of the poster presentations and publications are as follows:

ASCO Poster Presentations

Monday, June 3, 2024, 9:00am to 12:00pm CT
Abstract #: 6528
Title: Olutasidenib for Mutated IDH1 Acute Myeloid Leukemia: Final Five-Year Results from the Phase 2 Pivotal Cohort
Presenter: Jorge E. Cortes, M.D.

Abstract #: 6527
Title: Safety and Efficacy of Olutasidenib Treatment in Elderly Patients with Relapsed/Refractory mIDH1 Acute Myeloid Leukemia
Presenter: Stéphane de Botton, M.D., Ph.D.

Abstract #: TPS6591
Title: Phase 1b Trial of IRAK 1/4 Inhibition for Lower-Risk Myelodysplastic Syndrome Refractory/Resistant to Prior Therapies: A Trial in Progress
Presenter: Guillermo Garcia-Manero, M.D.

ASCO Publications

Abstract #: e18516
Title: Patients with Relapsed/Refractory mIDH1 AML Who Proceeded to Transplant After Olutasidenib Treatment
Authors: Stéphane de Botton, M.D., Ph.D.; Justin M Watts, M.D.; Brian A Jonas, M.D., Ph.D.; Mwe Mwe Chao, M.D.; Jorge Cortes, M.D.

Abstract #: e23289
Title: Real-World Experience with Fostamatinib in Patients with Immune Thrombocytopenia: Results of an Observational Study (FORTE)
Authors: Ruchika Goel, M.D., MPH; Waqas Azhar, M.D.; Robert P. Numerof, Ph.D.; Donna Chow, MS; Bhavesh Shah, M.D.

EHA2024 Congress abstracts may be accessed online via the EHA (Free EHA Whitepaper) Library. Details of the poster presentations and publications are as follows:

EHA Oral Presentation

Saturday, June 15, 17:30 to 17:45 CEST
Abstract #: S144
Title: Olutasidenib for Mutated IDH1 Acute Myeloid Leukemia: Final Five-year Results from the Phase 2 Pivotal Cohort
Presenter: Jorge E. Cortes, M.D.

EHA Poster Presentations

Friday, June 14, 18:00 to 19:00 CEST
Abstract #: P605
Title: Olutasidenib Demonstrates Clinical Activity in Mutated IDH1 Acute Myeloid Leukemia (AML) Secondary to Myeloproliferative Neoplasms (MPN)
Presenter: Stéphane de Botton, M.D., Ph.D.

Abstract #: P614
Title: Response to Olutasidenib in Patients with Acute Myeloid Leukemia (AML) Following Venetoclax Failure
Presenter: Jorge E. Cortes, M.D.

Abstract #: P611
Title: Safety and Efficacy of Olutasidenib Treatment in Elderly Patients with Relapsed/Refractory mIDH1 Acute Myeloid Leukemia
Presenter: Stéphane de Botton, M.D., Ph.D.

Abstract #: P1373
Title: Olutasidenib as Bridge-to-Transplant Treatment in Patients with Relapsed/Refractory mIDH1 Acute Myeloid Leukemia (AML)
Presenter: Stéphane de Botton, M.D., Ph.D.

EHA Publications

Abstract #: PB3344
Title: Real-World Experience with Fostamatinib in Patients with Immune Thrombocytopenia: Results of an Observational Study (FORTE)
Authors: Ruchika Goel, M.D., MPH; Drew Provan, M.D.; Francois Di Trapani, Pharm.D.

About AML
Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that there will be about 20,800 new cases in the United States, most in adults, in 2024.2

Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.3 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.4 Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed or refractory disease remain an unmet need.

About ITP
In patients with ITP (immune thrombocytopenia), the immune system attacks and destroys the body’s own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP are excessive bruising and bleeding. People suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death. Current therapies for ITP include steroids, blood platelet production boosters (TPO-RAs), and splenectomy. However, not all patients respond to existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP.

About R289
R289 is a prodrug of R835, an IRAK1/4 dual inhibitor, which has been shown in preclinical studies to block inflammatory cytokine production in response to toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) family signaling. TLRs and IL-1Rs play a critical role in the innate immune response and dysregulation of these pathways can lead to various inflammatory conditions. Chronic stimulation of both these receptor systems is thought to cause the pro-inflammatory environment in the bone marrow responsible for persistent cytopenias in lower-risk MDS patients.5

About REZLIDHIA

INDICATION
REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME

Differentiation syndrome, which can be fatal, can occur with REZLIDHIA treatment. Symptoms may include dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, hypotension, fever, and weight gain. If differentiation syndrome is suspected, withhold REZLIDHIA and initiate treatment with corticosteroids and hemodynamic monitoring until symptom resolution.

WARNINGS AND PRECAUTIONS

Differentiation Syndrome
REZLIDHIA can cause differentiation syndrome. In the clinical trial of REZLIDHIA in patients with relapsed or refractory AML, differentiation syndrome occurred in 16% of patients, with grade 3 or 4 differentiation syndrome occurring in 8% of patients treated, and fatalities in 1% of patients. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal. Symptoms of differentiation syndrome in patients treated with REZLIDHIA included leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, fever, edema, pyrexia, and weight gain. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption of REZLIDHIA. Differentiation syndrome occurred as early as 1 day and up to 18 months after REZLIDHIA initiation and has been observed with or without concomitant leukocytosis.

If differentiation syndrome is suspected, temporarily withhold REZLIDHIA and initiate systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours) for a minimum of 3 days and until resolution of signs and symptoms. If concomitant leukocytosis is observed, initiate treatment with hydroxyurea, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms. Differentiation syndrome may recur with premature discontinuation of corticosteroids and/or hydroxyurea treatment. Institute supportive measures and hemodynamic monitoring until improvement; withhold dose of REZLIDHIA and consider dose reduction based on recurrence.

Hepatotoxicity
REZLIDHIA can cause hepatotoxicity, presenting as increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased blood alkaline phosphatase, and/or elevated bilirubin. Of 153 patients with relapsed or refractory AML who received REZLIDHIA, hepatotoxicity occurred in 23% of patients; 13% experienced grade 3 or 4 hepatotoxicity. One patient treated with REZLIDHIA in combination with azacitidine in the clinical trial, a combination for which REZLIDHIA is not indicated, died from complications of drug-induced liver injury. The median time to onset of hepatotoxicity in patients with relapsed or refractory AML treated with REZLIDHIA was 1.2 months (range: 1 day to 17.5 months) after REZLIDHIA initiation, and the median time to resolution was 12 days (range: 1 day to 17 months). The most common hepatotoxicities were elevations of ALT, AST, blood alkaline phosphatase, and blood bilirubin.

Monitor patients frequently for clinical symptoms of hepatic dysfunction such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Obtain baseline liver function tests prior to initiation of REZLIDHIA, at least once weekly for the first two months, once every other week for the third month, once in the fourth month, and once every other month for the duration of therapy. If hepatic dysfunction occurs, withhold, reduce, or permanently discontinue REZLIDHIA based on recurrence/severity.

ADVERSE REACTIONS
The most common (≥20%) adverse reactions, including laboratory abnormalities, were aspartate aminotransferase increased, alanine aminotransferase increased, potassium decreased, sodium decreased, alkaline phosphatase increased, nausea, creatinine increased, fatigue/malaise, arthralgia, constipation, lymphocytes increased, bilirubin increased, leukocytosis, uric acid increased, dyspnea, pyrexia, rash, lipase increased, mucositis, diarrhea and transaminitis.

DRUG INTERACTIONS

Avoid concomitant use of REZLIDHIA with strong or moderate CYP3A inducers.
Avoid concomitant use of REZLIDHIA with sensitive CYP3A substrates unless otherwise instructed in the substrates prescribing information. If concomitant use is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
LACTATION
Advise women not to breastfeed during treatment with REZLIDHIA and for 2 weeks after the last dose.

GERIATRIC USE
No overall differences in effectiveness were observed between patients 65 years and older and younger patients. Compared to patients younger than 65 years of age, an increase in incidence of hepatotoxicity and hypertension was observed in patients ≥65 years of age.

HEPATIC IMPAIRMENT
In patients with mild or moderate hepatic impairment, closely monitor for increased probability of differentiation syndrome.

Click here for Full Prescribing Information, including Boxed WARNING.

To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088).

REZLIDHIA is a registered trademark of Rigel Pharmaceuticals, Inc.

About TAVALISSE
Indication
TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

Important Safety Information
Warnings and Precautions

Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required.
Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to ≥3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation.
Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE.
Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation.
TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose.
Drug Interactions

Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose.
It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406.
Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug.
Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug.
Adverse Reactions

Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%).
Common adverse reactions (≥5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.
Please see www.TAVALISSEUSPI.com for Full Prescribing Information.

To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088).

TAVALISSE is a registered trademark of Rigel Pharmaceuticals, Inc.