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Bolt Biotherapeutics Reports Interim BDC-1001 Phase 1/2 Data Demonstrating a Safe and Well-tolerated Profile and Emerging Clinical Activity at the ESMO Immuno-Oncology Congress 2021

On December 6, 2021 Bolt Biotherapeutics, Inc. (Nasdaq: BOLT), a clinical-stage biotechnology company pioneering a new class of immuno-oncology agents that combine the targeting precision of antibodies with the power of both the innate and adaptive immune systems, reported the presentation of interim clinical data from the company’s ongoing Phase 1/2 study of BDC-1001, the company’s lead immune-stimulating antibody conjugate (ISAC) in a poster session at the European Society for Medical Oncology Immuno-Oncology (ESMO I-O) Congress 2021, being held virtually from Dec. 6-11, 2021 (Press release, Bolt Biotherapeutics, DEC 6, 2021, View Source [SID1234596478]). The lead author for the poster is Manish Sharma, M.D., START Midwest, with contributions from Ecaterina Dumbrava, M.D., MD Anderson Cancer Center, and other colleagues from the U.S. and South Korea.

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The company reported data from 57 subjects participating in an ongoing Phase 1/2 study of BDC-1001, across 16 different types of HER2-expressing solid tumors. BDC-1001 demonstrated a favorable safety and tolerability profile at all evaluated doses and schedules, showing early signs of clinical activity with corresponding biomarker changes in the tumor microenvironment of post-treatment tumor biopsies. BDC-1001 is an immune-stimulating antibody conjugate (ISAC) comprising a HER2-targeting biosimilar of trastuzumab conjugated with a non-cleavable linker to an innovative TLR7/8 agonist.

"The favorable safety profile and early indications of clinical disease control in the BDC-1001 study are encouraging," said Dr. Sharma, Associate Director of Clinical Research at START Midwest. "There is a clear need for well tolerated, durable treatments in the fight against cancer and I’m excited to see if BDC-1001 can deliver on that potential as we explore higher drug exposure levels."

The poster presentation at ESMO (Free ESMO Whitepaper) I-O reported new safety, pharmacokinetic/pharmacodynamic, and efficacy results for the ongoing Phase 1 dose-escalation portion of the BDC-1001 monotherapy trial. Fifty-seven subjects have been treated at increasing dose levels up to 20 mg/kg every three weeks and 12 mg/kg every two weeks, and data from these subjects demonstrate that:

BDC-1001 continues to have a favorable safety and tolerability profile with mild (grade 1/grade 2) infusion related reactions in some patients and no dose-limiting toxicities at dose levels up to 20 mg/kg every three weeks and 12 mg/kg every two weeks. There was no indication of cytokine release syndrome (CRS), and a maximum tolerated dose (MTD) has not been reached.

Early signs of clinical activity are noted in 13 of 40 tumor evaluable subjects with one durable partial response maintained through 52 weeks and multiple subjects achieving stable disease for >12 weeks.

The pharmacokinetic (PK) data demonstrate increasing peak drug levels with increasing dose, and linearity of PK above the 5 mg/kg dose level. Clinical PK modeling predicts that target exposure levels can be achieved with weekly dosing.

Plasma and tissue biomarker results show increase in multiple biomarkers indicative of myeloid cell and TLR 7/8 activation that is consistent with BDC-1001’s mechanism of action. Increasing drug exposure correlates with increases in plasma cytokines and corresponding biomarker changes in the tumor microenvironment of multiple post-treatment tumor biopsies, with intriguing signs of clinical disease control.

These encouraging data point to the need for increased drug exposure to optimize clinical benefit. The favorable safety profile of BDC-1001 allows for continued enrollment in the dose escalation portion of the study, and the Company’s refined PK model based on data from more than 50 patients predicts that weekly administration will provide BDC-1001 exposures at or above the target exposure threshold. The data also support initiation of the combination therapy study with nivolumab (PD-1 inhibitor).

"Bolt Biotherapeutics is committed to agile clinical development based on data. In this Phase 1/2 study of BDC-1001, we have gained tremendous insight into the ability of this novel candidate to mobilize the patient’s immune system in targeting the tumor and its microenvironment. The increases in myeloid cell infiltration and repolarization of macrophages we’ve seen in multiple post-treatment biopsies are provocative and consistent with our proposed mechanism of action," said Edith Perez, M.D., Chief Medical Officer of Bolt Biotherapeutics. "We look forward to exploring weekly dosing as we get closer to determining the recommended Phase 2 dose for BDC-1001 as monotherapy, and to initiating combination therapy with a checkpoint inhibitor."

Presentation Details

Title: Preliminary results from a phase 1/2 study of BDC-1001, a novel HER2 targeting TLR7/8 immune-stimulating antibody conjugate (ISAC), in patients (pts) with advanced HER2-expressing solid tumors

Lead author: Manish R. Sharma, M.D.

Presentation Number: 164P

Timing: On-demand access beginning Dec. 6 at 12:00 p.m. CET.

The poster presentation will be available on the ESMO (Free ESMO Whitepaper) I-O conference website and on Bolt’s website.

Conference Call and Webcast Details

Bolt Biotherapeutics management will host a conference call for the investment community, in conjunction with the now virtual ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress 2021, to discuss emerging clinical data and insights from the ongoing Phase 1/2 study today, Monday, December 6, 2021, at 8:00 a.m. ET/5 a.m. PT.

The conference call can be accessed by dialing +1 (833) 665-0609 within the U.S. or Canada or by dialing +1 (929) 517-0400 from international locations. The passcode for the call is 2633068. A live webcast, including slides, will be available on the Events & Presentations page of Bolt Biotherapeutic’s website at www.boltbio.com. An archived replay can be accessed for 30 days following the webcast.

About the Boltbody Immune-Stimulating Antibody Conjugate (ISAC) Platform

ISACs are a new category of immunotherapy that combines the precision of antibody targeting with the strength of the innate and adaptive immune systems. Boltbody ISACs comprise three primary components: a tumor-targeting antibody, a non-cleavable linker, and a proprietary immune stimulant to activate the patient’s innate immune system. By initially targeting a single marker on the surface of a patient’s tumor cells, an ISAC can create a new immune response by activating and recruiting myeloid cells. The activated myeloid cells start a feed-forward loop by releasing cytokines and chemokines, chemical signals that attract other immune cells and lower the activation threshold for an immune response. This reprograms the tumor microenvironment and invokes an adaptive immune response that targets the tumor, with the goal of durable responses for patients with cancer.

Infinity Pharmaceuticals to Host an Investor Event on Updated MARIO-3 Data Presented at the 2021 San Antonio Breast Cancer Symposium

On December 6, 2021 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI), a clinical-stage biotechnology company developing eganelisib, a potentially first-in-class, oral, immuno-oncology macrophage reprogramming therapeutic that selectively inhibits phosphoinositide-3-kinase gamma (PI3K-gamma), reported that it will host an investor event on updated data from the ongoing MARIO-3 clinical study during the San Antonio Breast Cancer Symposium (SABCS 2021) on Friday, December 10th at 9:30 am ET (Press release, Infinity Pharmaceuticals, DEC 6, 2021, View Source [SID1234596477]).

The webinar will feature a presentation from Key Opinion Leader (KOL) Hatem Soliman, MD, MARIO-3 Investigator and Medical Director, Clinical Trials Office at the Moffitt Cancer Center.

Dr Soliman will discuss the evolving treatment landscape in TNBC and the significant unmet medical need that remains for patients with frontline, metastatic TNBC.
Importantly, Dr Soliman will review the MARIO-3 study design and summarize patient demographics and baseline characteristics as well as the updated safety and efficacy data from the MARIO-3 study.
Infinity’s Chief Medical Officer, Dr. Robert Ilaria, will review of eganelisib’s mechanism of action and translational data from the MARIO-3 study.

A Q&A session will follow the formal presentations. To register for the webinar please click here.

Hatem Soliman, MD is one of the leading breast cancer physicians in the country and an investigator on the MARIO-3 study. Dr. Soliman serves as the Medical Director of the Clinical Trials Office at the Moffitt Cancer Center, with extensive experience as a clinical investigator conducting both translational research in breast cancer immunotherapy and leading numerous clinical trials as principal investigator since joining the faculty at Moffitt in 2008. He also serves as the Course Director for the fellowship clinical research rotation, medical director of the phase 1 program, chair of Moffitt’s clinical research leadership council, chair of clinical research feasibility committee, and principal investigator for Moffitt’s CPDM CCSG application, which was recently rated as outstanding and awarded funding for an additional five years.

Dr. Soliman received his BS in Genetics from the University of Georgia Athens in 1996 and then went on to receive his medical degree from the Medical College of Georgia in 2002. His residency and fellowship training in oncology/hematology was completed through the University of South Florida/Moffitt Cancer Center program in 2008. During fellowship, he authored investigator initiated early phase trials with mentorship from Dr. Daniel Sullivan, former ACD and EVP of Moffitt, in collaboration with the NCI CTEP RAID program investigators Drs. Jaime Zwiebel and Howard Streicher. Upon graduation, Dr. Soliman was offered an assistant member position at Moffitt as a clinical investigator to continue early drug development and translational research activities.

Infinity Pharmaceuticals to Host an Investor Event on Updated MARIO-3 Data Presented at the 2021 San Antonio Breast Cancer Symposium

The webinar will feature a presentation from Key Opinion Leader (KOL) Hatem Soliman, MD, MARIO-3 Investigator and Medical Director, Clinical Trials Office at the Moffitt Cancer Center.

A Q&A session will follow the formal presentations. To register for the webinar please click here.

Corporate Presentation

On December 6, 2021 Bellicum Pharmaceuticals Presented the Corporate Presentation (Presentation, Bellicum Pharmaceuticals, DEC 6, 2021, View Source [SID1234596476]).

Kronos Bio Announces First Patient Dosed in AGILITY Phase 3 Clinical Trial of Entospletinib in Patients With Newly Diagnosed NPM1-mutated Acute Myeloid Leukemia

On December 6, 2021 Kronos Bio, Inc. (Nasdaq: KRON), a company dedicated to transforming the lives of those affected by cancer, reported that the first patient has been dosed in the registrational Phase 3 AGILITY clinical trial of entospletinib, a selective inhibitor targeting spleen tyrosine kinase (SYK), in combination with standard of care anthracycline and cytarabine (7+3) chemotherapy (Press release, Kronos Bio, DEC 6, 2021, View Source [SID1234596475]). This trial is the first in acute myeloid leukemia (AML) to use measurable residual disease (MRD) as the primary endpoint and has the potential to support accelerated approval of entospletinib by the U.S. Food and Drug Administration (FDA) as a treatment for patients newly diagnosed with NPM1-mutated AML who are fit for intensive induction.

"With the initiation of this trial, we are taking an important step forward for patients with AML, a form of blood cancer that has been difficult to treat historically," said Norbert Bischofberger, Ph.D., president and chief executive officer of Kronos Bio. "Even with current therapies, about half of people newly diagnosed with NPM1-mutated AML will die from the disease within five years. The use of the novel endpoint of MRD provides a pathway to potentially bring entospletinib to patients more quickly."

Entospletinib is Kronos Bio’s lead product candidate, and the company expects to share data from the trial in the second half of 2023. The randomized, double-blind, placebo-controlled trial is designed to assess the efficacy and safety of entospletinib in combination with intensive induction and consolidation chemotherapy in approximately 180 adults who have been newly diagnosed with NPM1-mutated AML. This trial will test the hypothesis, based on robust preclinical and Phase 2 clinical data, that NPM1 mutation leads to dependency on SYK signaling. The NPM1 mutation is present in about 30% of all adult patients with AML.

"We are pleased to be participating in this trial, with the goal of improving outcomes for patients with AML," said Karamjeet S. Sandhu, M.D., assistant professor in the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope, a world-renowned research and treatment organization near Los Angeles that was the first to dose a patient in the trial. "Patients with NPM1-mutated AML are in need of better treatment options, and we are excited that we are the first center to begin treating a patient in this trial."

The primary endpoint of the trial is MRD negative complete response (CR), as measured by molecular detection of mutant NPM1 alleles in bone marrow, which affords a high degree of sensitivity to detect MRD. Numerous clinical studies have shown that patients with NPM1 mutations who achieve MRD negative CR after induction chemotherapy survive longer than patients who achieve CR but have detectable MRD. If successful, this would be the first time MRD is used as the basis for seeking accelerated approval in AML.

The decision to proceed with this trial design was made after an End-of-Phase 2 discussion with the FDA. In the trial, patients will be randomized 1:1 to receive either entospletinib or placebo in combination with standard induction and consolidation chemotherapy. Remission and MRD status will be assessed after the first two cycles of chemotherapy and patients may receive up to a total of five cycles. Event-free survival (EFS) is a key secondary endpoint, and mature EFS data will potentially be used to support full approval.

Kronos Bio acquired entospletinib and another SYK inhibitor, lanraplenib, from Gilead Sciences in July 2020. As previously announced, under the agreement with Gilead, the initiation of the Phase 3 trial triggers a $29 million milestone payment from Kronos Bio to Gilead. The payment will be recorded in the fourth quarter.

Lanraplenib is being developed for the treatment of patients with relapsed/refractory FLT3-mutated AML and patients newly diagnosed with NPM1-mutated and/or FLT3-mutated AML who are older than 75 years old or are not eligible for intensive induction chemotherapy.

About Acute Myeloid Leukemia
Acute myeloid leukemia (AML) primarily affects adults and is one of the most difficult-to-treat blood cancers. AML starts in the bone marrow, impairing its ability to produce mature red blood cells, white blood cells and platelets. Without treatment, patients die within weeks to months from progressive bone marrow failure leading to infections, bleeding and heart failure. Approximately 20,000 people are diagnosed with AML in the United States each year, with the NPM1 genetic mutation found in approximately 30% of cases. Relapse in AML is common, and despite available treatments, nearly 11,000 people die from the disease each year in the United States.

About Measurable Residual Disease
Measurable residual disease (MRD) is a term that describes small numbers of leukemic cells that are still detectable during or after treatment, even when a patient has achieved complete response by standard criteria. Remaining leukemic cells in the body can become active and start to multiply, resulting in a relapse of the disease, which is fatal for most patients. Achieving MRD negativity, which is associated with longer remissions and improved survival, means that a treatment has reduced the number of leukemic cells to below the limit of detection by the most sensitive analytical methods. MRD can be detected using fluorescently labeled antibodies that recognize specific proteins on the surface of the leukemic cells (multi-parameter flow cytometry (MFC)) or by molecular methods such as DNA sequencing or polymerase chain reaction (PCR). Molecular methods are viewed as more sensitive and reliable than MFC, but require a unique mutation or DNA sequence that is only found in the leukemic cells. NPM1 mutations provide that unique sequence in patients with NPM1-mutated AML.

About Entospletinib
Kronos Bio is developing entospletinib for the frontline treatment of NPM1-mutated acute myeloid leukemia (AML). Entospletinib is a selective inhibitor targeting spleen tyrosine kinase (SYK), a critical node in a dysregulated transcription regulatory network within AML defined by persistent high expression of the transcription factors HOXA9 and MEIS1 (HOX/MEIS). Multiple AML driver mutations, including NPM1 and MLL gene rearrangements, have been associated with elevation of HOX/MEIS. Entospletinib has been investigated in more than 700 patients with a variety of hematologic malignancies, including AML, with clinical results observed in patients with AML who have NPM1 mutations and MLL rearrangements that support further development of the therapy.