On June 4, 2021 Glycotope GmbH, a biotechnology company developing antibodies against proteins carrying tumor-specific carbohydrate structures, reported it is presenting two posters at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which is being held virtually this year due to COVID-19 (Press release, Glycotope, JUN 4, 2021, View Source [SID1234583526]).

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Henner Kollenberg, Managing Director of Glycotope GmbH commented: "The data presented at ASCO (Free ASCO Whitepaper) highlight our ability to draw on our long-standing expertise in glyco-biology to generate novel biopharmaceuticals targeting cancer indications. The data showed that a Glycotope-developed anti-TA-MUC1 antibody combined with the anti-EGFR Tomuzotuximab or Panitumumab in patients with refractory solid tumors is safe and feasible and exhibited interesting anti-tumour activity."

Poster details are as follows:

Poster 2524

Title: Safety and tolerability results of the GATTO study, a phase Ib study combining the anti-TA-MUC1 antibody Gatipotuzumab with the anti-EGFR Tomuzotuximab or Panitumumab in patients with refractory solid tumors
Session: Poster Session: Developmental Therapeutics—Immunotherapy
Abstract ID: 332635

Download: View Source

Poster 2522
Title: Activity results of the GATTO study, a phase Ib study combining the anti-TA-MUC1 antibody Gatipotuzumab with the anti-EGFR Tomuzotuximab or Panitumumab in patients with refractory solid tumors

Session: Poster Session: Developmental Therapeutics—Immunotherapy
Abstract ID: 329709

On June 4, 2021 Kinnate Biopharma Inc. (Nasdaq: KNTE) ("Kinnate"), a biopharmaceutical company focused on the discovery and development of small molecule kinase inhibitors for difficult-to-treat, genomically defined cancers, reported that results from preclinical studies evaluating its lead RAF inhibitor candidate, KIN-2787 (Press release, Kinnate Biopharma, JUN 4, 2021, View Source [SID1234583524]). These data will be presented today during a virtual poster session at the 57th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper).

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KIN-2787, Kinnate’s most advanced product candidate, is an orally available small molecule pan-RAF inhibitor being developed for the treatment of patients with lung cancer, melanoma, and other solid tumors. Unlike currently available treatments that target only Class I BRAF kinase mutations, Kinnate has designed KIN-2787 to target Class II and Class III BRAF mutations, where it would be a first-line targeted therapy, in addition to covering Class I BRAF mutations. The U.S. Food and Drug Administration (FDA) has cleared Kinnate’s Investigational New Drug (IND) application for KIN-2787 and the company anticipates initiating a first-in-human Phase 1 clinical trial of the candidate in patients with mutant BRAF-driven solid tumors in mid-2021.

"These data are important, early signals of the potential anti-tumor activity of KIN-2787 and support our IND application recently cleared by the FDA," said Eric Murphy, PhD, Chief Scientific Officer, and co-founder of Kinnate. "Our approach targets dimer signaling in specific patient populations with BRAF mutations while minimizing MAPK paradoxical activation. KIN-2787 shows pronounced in vitro and in vivo activity against human cancers driven by Class I, II and III BRAF alterations, and these results support our phase 1 clinical trial initiating shortly in these defined molecular subtypes."

The poster presentation, delivered by Aleksandra Franovic, PhD, Senior Director of Translational Medicine at Kinnate, highlights data which show that treatment with KIN-2787 resulted in exposure-dependent inhibition of MEK-ERK phosphorylation and was accompanied by the successful suppression of MAPK transcriptional targets at the RNA and protein level. High selectivity was displayed for all three RAF family kinases in screens evaluating its activity against more than 600 kinases. Due to potent dimer inhibition, KIN-2787 did not demonstrate significant paradoxical activation in these studies. Twice daily (BID) dosing was well-tolerated and led to prolonged target coverage and a trend towards more frequent and deeper tumor responses in vivo.

Kinnate’s poster presentation (Abstract #3116), titled "The next-generation pan-RAF inhibitor, KIN-2787, is active in class II and class III BRAF Mutant models," will be available for on-demand viewing at 09:00AM ET today and can be accessed via: View Source

On June 4, 2021 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported that it will host a virtual KOL event to discuss progress to date for CA-4948, a first-in-class IRAK4 kinase inhibitor, including updated data presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2021 Virtual Congress from the Phase 1/2 study of CA-4948 in patients with AML or high-risk MDS (Press release, Curis, JUN 4, 2021, View Source [SID1234583523]). The event will be held on Friday, June 11, 2021 at 8:00 am ET.

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The event will be led by James Dentzer, President and CEO, and will include a presentation by Dr. Guillermo Garcia-Manero, M.D., Chief of the Section of Myelodysplastic Syndromes within the Department of Leukemia at the University of Texas MD Anderson Cancer Center. The speakers and additional members of Curis leadership will be available to answer questions at the end of the event.

A live webcast of the presentation will be available under "Events & Presentations" in the Investors section of the Company’s website at www.curis.com. A replay of the webcast will be available on the Curis website for approximately 90 days following the event.

On June 4, 2021 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that new data on its investigational CD20xCD3 T-cell engaging bispecific antibodies, mosunetuzumab and glofitamab, and its first-in-class anti-CD79b antibody-drug conjugate, Polivy (polatuzumab vedotin), in non-Hodgkin lymphoma (NHL) will be presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting from 4-8 June 2021 (Press release, Hoffmann-La Roche, JUN 4, 2021, View Source [SID1234583522]).

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"People with difficult-to-treat blood cancers such as non-Hodgkin lymphoma still need more options to help improve outcomes," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "We are encouraged by promising data from our emerging T-cell engaging bispecific antibodies, mosunetuzumab and glofitamab, and the antibody-drug conjugate, Polivy, that demonstrate the potential of these novel immunotherapeutic approaches for various groups of patients."

While approximately 500,000 people worldwide are diagnosed with NHL each year, treatment options are currently limited and resistance to existing therapies or relapse following treatment is common.1 The most prevalent form of NHL, accounting for about 40% of newly diagnosed NHL cases, is an aggressive form called diffuse large B-cell lymphoma (DLBCL), that comes with a life expectancy of weeks or months if left untreated.2,3

In clinical trials to date, the investigational CD20xCD3 T-cell engaging bispecific antibodies, mosunetuzumab and glofitamab, have shown promising responses across multiple types of NHL, including relapsed or refractory (R/R) DLBCL and follicular lymphoma (FL). Pivotal data for these medicines are expected this year and Roche is targeting a regulatory filing for mosunetuzumab in FL by the end of 2021, following its U.S. Food and Drug Administration Breakthrough Therapy Designation granted in June 2020. Key data on mosunetuzumab and glofitamab to be presented at the meeting include:

Phase I NP30179 study investigating step-up dosing of glofitamab in heavily pre-treated R/R NHL, showed high, ongoing complete responses (CRs) and an acceptable safety profile. After a median follow-up of 6.3 months, results showed that glofitamab achieved a complete metabolic response rate, defined as the disappearance of metabolic tumour activity, of 71.4% in patients with aggressive (fast-growing) NHL. The most common adverse events (AEs) were cytokine release syndrome (CRS) (63.5%), neutropenia (38.5%), and pyrexia (32.7%); CRS events were mostly low grade and confined to the first cycle of treatment.4
Phase I/II GO40516 study of mosunetuzumab in combination with Polivy in R/R NHL showed promising efficacy and an acceptable safety profile. The regimen achieved a CR of 54.5% in all patients. Eighty six percent of patients evaluated had aggressive NHL, and these patients achieved a CR rate of 47.4%. The most frequent treatment-related AEs were neutropenia (45.4%), fatigue, nausea, and diarrhoea (all 36.4%) and CRS (9.1%; all Grade 1).5
Broad development programmes are ongoing for mosunetuzumab and glofitamab, including the phase III GO42909 trial investigating mosunetuzumab plus lenalidomide versus MabThera/Rituxan (rituximab) plus lenalidomide in R/R FL, which will soon be enrolling patients. For glofitamab, the phase III GO41944 open-label, randomised trial designed to evaluate the safety and efficacy of glofitamab plus gemcitabine and oxaliplatin (glofit-GemOx) versus MabThera/Rituxan plus GemOx in patients with R/R DLBCL, is also ongoing.

Roche is committed to pursuing treatment solutions that can be tailored to meet the various needs of both people living with NHL and healthcare professionals. Polivy is already a treatment option for people with R/R DLBCL and continues to show potential in multiple combinations. Key data at the meeting include:

New triplet combination of Polivy with MabThera/Rituxan and lenalidomide, which demonstrated promising activity in difficult-to-treat R/R DLBCL, based on results from the phase Ib/II GO29834 study. With a median follow-up of 9.7 months, median overall survival was 10.9 months (95% CI: 7.4–NE) and median progression-free survival was 6.3 months (95% CI: 4.5–9.7) in patients treated with the triplet. The most commonly reported Grade 3-4 AEs were neutropenia (58.0%), thrombocytopenia (14.0%), infections (14.0%) and anaemia (11.0%).6

As a leader in haematology development, Roche will continue to follow the science to expand and improve upon treatment options for healthcare providers and people with difficult-to-treat blood cancers.

Keep up to date with ASCO (Free ASCO Whitepaper) news and updates by using the hashtag #ASCO21 and follow Roche on Twitter via @Roche and on LinkedIn.

About Roche’s investigational bispecifics in haematology
Roche is currently developing two T-cell engaging bispecific antibodies, mosunetuzumab and glofitamab, designed to target CD20 on the surface of B-cells and CD3 on the surface of T-cells. This dual targeting activates and redirects a patient’s existing T-cells to engage and eliminate target B-cells by releasing cytotoxic proteins into the B-cells. Mosunetuzumab and glofitamab differ in their structures, and both are being developed by Roche as part of our ongoing strategy to explore multiple bispecific formats, to identify those that maximise potential clinical benefits for patients. Mosunetuzumab has a structure similar to that of a natural human antibody in that it has two ‘Fab’ regions, but is different from naturally-occurring antibodies in that one ‘Fab’ region targets CD20 and the other ‘Fab’ region targets CD3. Glofitamab is based on a novel structural format called ‘2:1’, which refers to the structure of the antibody. It is engineered to have two ‘Fab’ regions which bind to CD20, and one ‘Fab’ region which binds to CD3. The clinical development programmes for mosunetuzumab and glofitamab include ongoing investigations of these molecules as monotherapies and in combination with other medicines, for the treatment of people with CD20-positive B-cell non-Hodgkin lymphomas (NHL), including diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).

About Polivy (polatuzumab vedotin)
Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B-cells, an immune cell impacted in some types of NHL, making it a promising target for the development of new therapies.7,8 Polivy binds to CD79b and destroys these B-cells through the delivery of an anti-cancer agent, which is thought to minimise the effects on normal cells.9,10 Polivy is being developed by Roche using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL. Polivy is marketed in the US by Genentech as Polivy (polatuzumab vedotin-piiq), with piiq as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration.

About the NP30179 study
The NP30179 study [NCT03075696] is a phase I/Ib, multicentre, open-label, dose-escalation study, evaluating the efficacy, safety, tolerability and pharmacokinetics of glofitamab. In this study, glofitamab is assessed as a single-agent and in combination with Gazyva/Gazyvaro (obinutuzumab), following pre-treatment with a one-time, fixed-dose of Gazyva/Gazyvaro, in people with relapsed or refractory (R/R) B-cell NHL. Outcome measures include overall response rate, complete response rate per Lugano 2014 criteria, maximum tolerated dose and tolerability.

About the GO40516 study
The GO40516 study [NCT03671018] is a phase I/II, multicentre, open-label study, evaluating the efficacy, safety, tolerability and pharmacokinetics of mosunetuzumab in combination with Polivy in people with B-cell NHL. It consists of a dose finding portion followed by an expansion phase for second line or later (2L+) participants with R/R DLBCL and 2L+ R/R FL. Outcome measures include best overall response rate, maximum tolerated dose and tolerability.

About the GO29834 study
The GO29834 study [NCT02600897] is a phase Ib/II, multicentre, open-label study, evaluating the efficacy and safety of Polivy with MabThera /Rituxan (rituximab) and lenalidomide in R/R DLBCL. Outcome measures include complete response and tolerability.

About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for over 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera/Rituxan, Gazyva/Gazyvaro, Polivy, Venclexta/Venclyxto (venetoclax) in collaboration with AbbVie, and Hemlibra (emicizumab). Our pipeline of investigational haematology medicines includes T-cell engaging bispecific antibodies, glofitamab and mosunetuzumab, targeting both CD20 and CD3, and cevostamab, targeting FcRH5 and CD3; Tecentriq (atezolizumab), a monoclonal antibody designed to bind with PD-L1; and crovalimab, an anti-C5 antibody engineered to optimise complement inhibition. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.

On June 4, 2021 Precision BioSciences Inc. (Nasdaq: DTIL), a clinical stage biotechnology company developing allogeneic CAR T and in vivo gene correction therapies with its ARCUS genome editing platform, reported encouraging progress on two strategies designed to optimize the durability of allogeneic CAR T therapy in patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) (Press release, Precision Biosciences, JUN 4, 2021, View Source [SID1234583521]). The Company reported updated interim results from its Phase 1/2a study of PBCAR0191, the Company’s investigational, off-the-shelf, allogeneic CAR T cell therapy targeting CD19. As of May 21, 2021, 12 patients with R/R NHL were enrolled and evaluated for response to PBCAR0191 with enhanced lymphodepletion (eLD). The Company also reported preclinical data demonstrating the potential mechanism by which its investigational immune evading stealth cell, PBCAR19B, may avoid rejection by T cells and natural killer (NK) cells.

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"These interim results in heavily pretreated R/R NHL patients illustrate the potential for PBCAR0191 to recognize and target CD19 positive cancer cells and suggest that enhanced lymphodepletion may be a strategy to help suppress host immune rejection. We’re encouraged by the high initial response rates and look forward to monitoring the responses for evidence of long-term durability," said Alan List, MD, Chief Medical Officer of Precision BioSciences. "In addition, our PBCAR19B Phase 1 study is open for enrollment, and we believe this candidate has the potential to build on the encouraging clinical responses we’ve seen with PBCAR0191 to date and reduce the need for prolonged immunosuppression."

As of May 21, 2021, 18 subjects in the Phase 1/2a study of PBCAR0191 with R/R NHL completed Day 28 evaluation and received either eLD1 (n=12) or standard lymphodepletion2 (sLD; n=6) with Dose Level 33 of PBCAR0191.

Efficacy

Use of eLD mitigated PBCAR0191 rejection and markedly increased peak cell expansion (~72x) and area under the curve (AUC) (~59x), each as compared to sLD.
A single dose of PBCAR0191 cells following eLD yielded clinical responses in the majority of patients, with overall response rates (ORR) and complete response (CR) rates of 75% and 50%, respectively at Day ≥ 28.
Five of nine responding patients (56%) who received PBCAR0191 cells following eLD remained progression-free, including 4/9 evaluable subjects with responses lasting > 4 months. Assessment of duration of response is on-going.
Median interval from confirmation of eligibility to start of LD was 1 day, reinforcing the potential feasibility for rapid delivery of off-the-shelf, allogeneic, cellular therapy for high-risk patients.
Day ≥ 28 Evaluation

* Three of four responding patients had prior auto-SCT and auto CD19 CAR treatment.

Safety and Tolerability

As of May 21, 2021, PBCAR0191 with eLD continued to show acceptable tolerability without evidence of graft versus host disease (GvHD) and with a similar frequency of immune effector cell-associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS) compared to patients who received sLD. Infections occurred more frequently when PBCAR0191 was dosed following eLD.

Adverse Event Max Grade

(Graft versus host disease)

Three treatment emergent deaths without disease progression occurred, including two cases of infection and one case of cardiac arrest after a choking incident. Two of these patients were in ongoing complete responses at time of death. Only one death, as previously reported on December 4, 2020 was assessed by the investigator as possibly related to study treatment.

Demographics for Enrolled R/R NHL Patients (PBCAR0191 with eLD)

Over 80% of subjects had advanced and aggressive lymphomas.
75% had stage III/IV disease.
Subjects had received a median of seven lines of therapy prior to study enrollment.
33% of subjects had prior CD19-directed CAR therapy.
PBCAR19B Immune Evading Stealth Cell

PBCAR19B is designed to extend persistence of allogeneic CAR T cells by evading rejection by the immune system of the patient. In preclinical studies, the anti-CD19 PBCAR19B stealth cell exhibited substantial resistance to rejection mediated by both allo-reactive T cell and NK cells, suggesting the potential utility of this approach.

In January 2021, Precision announced that the U.S. Food and Drug Administration accepted its investigational new drug application to evaluate the safety and clinical activity of PBCAR19B in patients with R/R NHL. Initial clinical trial sites have been selected for the Phase 1 study that is now open for enrollment. PBCAR19B will be evaluated at increasing flat dose levels beginning at 2.7 x 108 cells using sLD with the ability to dose up to 8.1 x 108 cells. Of note, the first dose level is approximately equivalent to Dose Level 3 in the PBCAR0191 trial.

Company-Hosted Conference Call and Web Cast Information

Precision will host a conference call and webcast today, Friday, June 4, 2021 at 8:00 a.m. ET to discuss the most recent interim clinical data for PBCAR0191 and preclinical data for PBCAR19B. The dial-in conference call numbers for domestic and international callers are (866) 996-7202 and (270) 215-9609, respectively. The conference ID number for the call is 5647916. Participants may access the live webcast and the accompanying presentation materials on Precision’s website www.precisionbiosciences.com in the Investors and Media section under Events and Presentations. An archived replay of the webcast will be available on Precision’s website.

About PBCAR0191 and Study Design (Clinical Trials Study Identifier: NCT03666000)

PBCAR0191 is an investigational allogeneic chimeric antigen receptor T cell therapy (CAR T) in a Phase 1/2a trial for the treatment of patients with R/R NHL and R/R B-ALL. PBCAR0191 was designed using Precision BioSciences novel and proprietary ARCUS genome editing platform. It has been granted Fast Track Designation by the FDA for B-ALL. Precision also holds Orphan Drug Designation from the FDA for this program in mantle cell lymphoma, an aggressive subtype of NHL.

About PBCAR19B (Clinical Trials Study Identifier: NCT04649112)

PBCAR19B is a next-generation, stealth cell candidate for patients with CD19-positive malignancies such as R/R NHL. PBCAR19B is designed to improve the persistence of allogeneic CAR T cells following infusion by reducing rejection by T cells and NK cells. In addition to the CAR gene, the PBCAR19B stealth cell vector carries a short hairpin RNA that suppresses expression of beta-2 microglobulin, a component of Major Histocompatibility Complex (MHC) Class I molecules found on the cell surface. Reducing or knocking-down Class I MHC expression on allogeneic CAR T cells has been shown to reduce CAR T cell killing by cytotoxic allo-reactive T cells. Additionally, in an effort to attenuate NK cell-mediated elimination due to MHC class I knockdown, the PBCAR19B vector also carries an HLA-E gene designed to inactivate NK cells.