Mersana Therapeutics Announces Initiation of UPLIFT Single-Arm Registration Strategy for UpRi in Platinum-Resistant Ovarian Cancer

On April 9, 2021 Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported the initiation of patient dosing in UPLIFT, a single-arm registration strategy to evaluate the safety and efficacy of upifitamab rilsodotin (UpRi, XMT-1536) in patients with platinum-resistant ovarian cancer who have received up to four lines of therapy (Press release, Mersana Therapeutics, APR 9, 2021, View Source [SID1234577790]).

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"UpRi has demonstrated clinically meaningful activity, a biomarker-response relationship and a differentiated tolerability profile without severe neutropenia, peripheral neuropathy or ocular toxicity in heavily pretreated ovarian cancer patients who have limited options and poor prognosis. The UPLIFT strategy is critical to bringing this promising agent to patients waiting for new therapies," said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics.

UPLIFT will evaluate the safety and efficacy of UpRi in patients with platinum-resistant ovarian cancer who have received up to four lines of therapy. Consistent with the bevacizumab label, patients previously treated with three or four lines of therapy may enroll without regard to prior bevacizumab treatment. There is no exclusion for patients with baseline peripheral neuropathy. Patients may enroll without regard to NaPi2b expression; however, the role of the biomarker will be evaluated. The primary endpoint will be the objective response rate (ORR) in the high NaPi2b population and the secondary endpoints will be the ORR regardless of NaPi2b expression, as well as duration of response and safety.

"We believe this study design, which is an amendment to the ongoing Phase 1 expansion study, allows for significant operational efficiencies and leverages our current momentum in patient enrollment. The study design also allows us the opportunity to fully evaluate the role of the biomarker with endpoints in both the high NaPi2b and overall populations. We are excited to open this cohort to this heavily pretreated patient population with few options," said Arvin Yang, M.D., Ph.D., Senior Vice President and Chief Medical Officer of Mersana Therapeutics.

The single-arm registration strategy is an amendment to the ongoing multinational, multi-center, open label study protocol, and the Company expects to enroll approximately 100 patients with high NaPi2b expression and up to 180 patients overall.

Seagen to Highlight Data from Novel Targeted Therapies at AACR

On April 9, 2021 Seagen Inc. (Nasdaq: SGEN) reported that preclinical data from its pipeline of novel targeted oncology drugs will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held April 10-15, 2021 (Press release, Seagen, APR 9, 2021, View Source [SID1234577789]). The oral and poster presentations will highlight several early-stage programs utilizing Seagen’s leading antibody-drug conjugate (ADC) technology as well as its proprietary sugar-engineered antibody (SEA) technology.

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"Our research being presented at AACR (Free AACR Whitepaper) describes intriguing preclinical data for three novel pipeline programs that are in ongoing clinical trials. This includes SEA-TGT, an anti-TIGIT antibody using our SEA technology, and two vedotin-based ADCs, SGN-B6A and SGN-STNV. We believe these three programs represent potential best-in-class or first-in-class targeted therapies for cancer," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "Among the findings, we will show the enhanced therapeutic effect in combining SEA-TGT with a checkpoint inhibitor or a vedotin-based ADC across different tumor models. In addition, we will report for the first time our preclinical data with SGN-STNV, a novel ADC targeting a carbohydrate antigen that may have broad applicability across solid tumors."

Highlights of Seagen Programs Presented at AACR (Free AACR Whitepaper)

SEA-TGT

Preclinical data will be presented for SEA-TGT, a novel investigational nonfucosylated human IgG1 TIGIT antibody, which utilizes Seagen’s proprietary SEA technology that enhances functionality by targeting key immune activating Fc receptors. TIGIT is an inhibitory immune checkpoint that has emerged as a clinically relevant immuno-oncology target. The monotherapy and combinatorial activity of SEA-TGT was assessed and compared to TIGIT monoclonal antibodies (mAbs) with inert, standard, or effector function modified backbones in vivo and in vitro. Key preclinical findings were as follows:

the SEA-TGT backbone was distinct as it increased binding to activating FcγRIIIa with minimal binding to inhibitory FcγRIIb;
the empowered backbone had superior therapeutic properties including enhanced depletion of TIGIT-positive regulatory T-cells and activation of antigen-presenting cells both of which are important in promoting antitumor activity;
SEA-TGT demonstrated enhanced antitumor activity both as a single agent and in combination with anti-PD1 therapy; and,
SEA-TGT produced an enhanced therapeutic effect when combined with an immunogenic tumor cell death-inducing vedotin ADC.
A phase 1 trial evaluating SEA-TGT alone and in combination with anti-PD-1 therapy in patients with advanced solid tumors and select lymphomas is ongoing.

SGN-B6A

Preclinical data will also be presented on SGN-B6A, an investigational ADC targeting integrin beta-6, which is overexpressed in numerous solid tumors and has been demonstrated to be a negative prognostic indicator across a diverse range of cancers, including non-small cell lung cancer (NSCLC). Data demonstrate SGN-B6A is active when dosed weekly in patient-derived xenograft models of NSCLC, representing both squamous and adenocarcinoma histology. A phase 1 trial evaluating monotherapy SGN-B6A in advanced solid tumors is ongoing.

SGN-STNV

SGN-STVN is an investigational ADC with a unique mechanism for targeting a carbohydrate antigen called Sialyl-Thomsen nouveau (STn), which is highly expressed on a variety of solid tumors including non-small cell lung, ovarian and gastric cancers. The preclinical data demonstrate SGN-STNV is highly specific for STn independent of protein identity, which could allow for the targeting of a range of tumor types that express different glycoproteins. In xenograft studies across key tumor types, the specificity and ability to target STn on multiple tumor-associated proteins led to durable tumor regressions. SGN-STNV was well-tolerated in in vivo studies and is being evaluated in an ongoing phase 1 study.

Additional Details of Seagen Presentations at AACR (Free AACR Whitepaper) Annual Meeting 2021

All poster presentations will be available via on-demand view starting on April 10 at 8:30 a.m. Eastern Time. Oral symposium presentations will be available at the beginning of the session where the study is presented.

Abstract Title

Abstract #

Date

Presenter

Oral

Targeting Sialyl-Thomsen nouveau (STn) antigen with the SGN-STNV antibody-drug conjugate is effective in preclinical studies

#50

April 10 in session at 4:00 – 6:00 p.m. ET

A. Schwartz

E-Poster

SEA-TGT is an empowered anti-TIGIT antibody that displays superior combinatorial activity with several therapeutic agents

#1583

April 10

A. Smith

Activity of SGN-B6A in patient-derived xenograft models of non-small cell lung cancer

#914

April 10

R. Lyon

Pharmacokinetics of tucatinib in healthy and hepatically-impaired volunteers

#1371

April 10

A. Topletz-Erickson

Precision BioSciences to Participate in the Truist Securities 2021 Life Sciences Virtual Series

On April 9, 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 that Derek Jantz, Ph.D., Chief Scientific Officer and Co-Founder will participate in a fireside chat at the Truist Securities 2021 Life Sciences Virtual Series (Press release, Precision Biosciences, APR 9, 2021, View Source [SID1234577788]).

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Details for the fireside chat are below:

The Truist Securities 2021 Life Sciences Virtual Series
Date: Tuesday, April 13, 2021
Time: 11:00 AM ET

A live webcast of the fireside chat will be accessible on the Company’s website www.precisionbiosciences.com, under the Investors & Media section. An archived replay of the webcasts will be available for approximately 30 days following the presentations.

Surface Oncology Presents Promising Preclinical Data for Lead Immunotherapy Product Candidates at the American Association for Cancer Research Annual Meeting

On April 9, 2021 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported that it will present preclinical findings supporting the company’s lead product programs, SRF388 (targeting IL-27) and SRF617 (targeting CD39) (Press release, Surface Oncology, APR 9, 2021, View Source [SID1234577786]). These data will be presented as part of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2021 Annual Meeting, which is being held virtually April 10-15 and May 17-21, 2021.

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"These findings further support the biological rationale that both of our lead product candidates, SRF388 and SRF617, promote increased proinflammatory activity within the tumor microenvironment in the hopes of ultimately providing novel treatment options to patients with cancer," said Vito Palombella, chief scientific officer. "We look forward to sharing data from the ongoing Phase 1 clinical trials for both programs this June."

The e-poster website will be launched at 8:30 a.m. ET on Saturday, April 10, and will remain available for viewing through Monday, June 21. The two e-posters will also be viewable on the Surface Oncology website.

Presentation Type: e-poster (Abstract: 1802)
Title: CD39 inhibition shapes the transcriptional landscape of myeloid cells and induces proinflammatory states in the CT26 syngeneic tumor model
Lead Authors: Devapregasan Moodley, Ph.D. and Mayra Carneiro

Summary:

SRF617 is a potent inhibitor of CD39 enzymatic activity both in vitro and in vivo.
Increased activity of CD39 results in significant reductions in extracellular ATP and subsequent accumulation of adenosine, contributing to tumor immune escape, induction of angiogenesis and metastatic progression.
Immunological mechanisms associated with CD39 blockade reveal major changes to immunocyte transcriptional landscapes, including upregulation of several proinflammatory genes.
CD39 inhibition predominantly shaped the transcriptional landscape of myeloid cells and dendritic cells, and generally induced proinflammatory conditions.
These findings indicate that CD39 blockade induces proinflammatory responses, supporting future clinical studies of SRF617 for treating patients with cancer.
Presentation Type: e-poster (Abstract: 1607)
Title: IL-27 signaling serves as an immunological checkpoint for NK cells to promote hepatocellular carcinoma in multiple murine models
Lead Author: Turan Aghayev

Summary:

IL-27 signaling suppresses natural killer (NK) cells within the tumor microenvironment, promoting hepatocellular carcinoma (HCC) development in vivo.
Elevated IL-27RA expression in cancer tissue and elevated EBI3 serum levels are associated with poor prognosis in patients with HCC.
Inhibiting IL-27 signaling leads to tumor growth inhibition and suppressed HCC development in a non-alcoholic steatohepatitis (NASH)-driven HCC model with concomitant enhancement of NK cell activity.
These findings indicate that IL-27 blockade regulates NK cell-mediated control of HCC and is a promising therapeutic target in liver cancer.
About SRF617:
SRF617 is a fully human antibody designed to inhibit the enzymatic activity of CD39, allowing for a dual mechanism of action to promote anti-tumor immunity via reduction of immunosuppressive adenosine in addition to increasing levels of immunostimulatory ATP. A substantial body of research supports a role for CD39 in allowing cancer to evade immune responses. For example, pancreatic cancer stromal cells within the tumor micro-environment express high levels of CD39 which may inhibit anti-cancer immune responses. In preclinical studies, SRF617 has exhibited strong affinity for and inhibition of CD39, the ability to reduce adenosine and increase ATP levels and anti-tumor activity both as a single agent and in combination with multiple therapeutic agents.

About SRF388:
SRF388 is a fully human anti-IL-27 antibody designed to inhibit the activity of this immunosuppressive cytokine. Surface Oncology has identified particular tumor types, including liver and kidney cancer, where IL-27 appears to play an important role in the immunosuppressive tumor microenvironment and may contribute to resistance to treatment with checkpoint inhibitors. SRF388 targets the rate-limiting p28 subunit of IL-27, and preclinical studies have shown that treatment with SRF388 blocks the immuno-suppressive biologic effects of IL-27, resulting in immune cell activation in combination with other cancer therapies including anti-PD-1 therapy, as well as potent anti-tumor effects as a monotherapy. Furthermore, Surface Oncology has identified a potential biomarker associated with IL-27 that may be useful in helping to identify patients most likely to respond to SRF388. In November 2020, Surface announced that SRF388 was granted Orphan Drug designation and Fast Track designation for the treatment of hepatocellular carcinoma from the FDA.

Affimed Announces Presentation at AACR Highlighting Initial Data from Phase 1 Study of Cord Blood-derived Natural Killer Cells Pre-complexed with Innate Cell Engager AFM13

On April 9, 2021 Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported that positive initial clinical data from an investigator-sponsored study at The University of Texas MD Anderson Cancer Center evaluating cord blood-derived natural killer (cbNK) cells pre-complexed with Affimed’s innate cell engager (ICE) AFM13 (CD16A/CD30) (Press release, Affimed, APR 9, 2021, View Source [SID1234577785]).

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This approach was developed in the laboratory of Katy Rezvani, M.D., Ph.D., Professor of Stem Cell Transplantation and Cellular Therapy at MD Anderson, who is presenting the data as part of the Major Symposia and Advances sessions at the virtual American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. The presentation is available for viewing by registered participants through June 21, 2021. Dr. Rezvani will take part in a live panel discussion as part of the presentation on April 13, 2021 at 1:30 p.m. EDT.

"We are encouraged by the initial safety and efficacy data from this groundbreaking first in-human study. The finding of an objective response rate of 100% amongst our first four patients enrolled is impressive," said Andreas Harstrick, M.D., Chief Medical Officer of Affimed. "These initial results indicate AFM13 may have the potential to help NK cells target and destroy cancer cells. We plan to continue to develop and customize approaches that leverage the unique and differentiating features of our ICE molecules in combination with adoptive NK cell transfer to provide options for treating a variety of hematologic and solid tumors."

The open-label, non-randomized, single-center, dose-escalation trial is evaluating the pre-complexing of AFM13 with cbNK cells followed by three weekly infusions of AFM13 monotherapy in adult patients with recurrent/refractory CD30-positive lymphomas. The trial is led by Yago Nieto, M.D., Ph.D., Professor of Stem Cell Transplantation and Cellular Therapy at MD Anderson.

"There remains a high unmet need for effective treatments in relapsed/refractory (R/R) CD30+ lymphomas. We are encouraged by the data generated from the first patients treated with cbNK cells pre-complexed with AFM13," said Dr. Rezvani. "The results suggest this combination is facilitating clinical responses with minimal toxicity, warranting further study as we continue to explore novel cell therapies for our patients."

LOGO

As of March 31, 2021, three patients have been dosed with two cycles of therapy in dose cohort 1 (1×106 AFM13-cbNK/kg) and one patient has received a single cycle of therapy in dose cohort 2 (1×107 AFM13-cbNK/kg). The study is currently enrolling patients in the second dose cohort of NK cells, and further updates are expected later in 2021. Results from the first cycle of the first dose cohort are being presented by Dr. Rezvani at AACR (Free AACR Whitepaper), and Affimed is supplementing the data with best responses as of March 31, 2021, as summarized below.

Patient

number
cbNK Cell
Dose


Patient


Cancer Type


Prior Treatment


CRS/

Neurotoxicity/

GVHD


Best Response

Cohort 1 – completed
#1 1×106 / kg 43-year-old-male Hodgkin lymphoma 4 lines of therapy (ABVD, ICE, brentuximab vedotin, nivolumab + ruxolitinib) None Partial response
#2 1×106 / kg 31-year-old-male Hodgkin lymphoma 14 lines of therapy (ABVD, brentuximab vedotin, HDACi/P13Ki, pembrolizumab, nivolumab, allo-HSCT, hypercytoxan, ibrutinib, niraparib, bendamustine, everolimus) None Partial response
#3 1×106 / kg 53-year-old-female Hodgkin lymphoma 5 lines of therapy (ABVD, ICE, brentuximab vedotin, nivolumab, GemOx) None Complete response after cycle 2
Cohort 2 – ongoing (1 of 3 patients enrolled)
#4 1×107 / kg 26-year-old-male Hodgkin lymphoma 9 lines of therapy (ABVD, ICE + brentuximab vedotin, radiation, nivolumab, CD30-CART, TTI-622, brentuximab vedotin + bendamustine, allo-HSCT, brentuximab vedotin + bendamustine with brentuximab vedotin maintenance) None Complete response
ABVD = Adriamycin (doxorubicin), Bleomycin, Vinblastine, Dacarbazine (DTIC)

ICE = chemotherapy combination includes the drugs: ifosfamide, carboplatin, & etoposide phosphate

GemOx= gemcitabine, oxaliplatin

There were no observed events of cytokine release syndrome, neurotoxicity syndrome or graft-versus-host disease.

Response evaluation followed the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC). All four patients had relapsed/refractory Hodgkin Lymphoma and were heavily pretreated, with between 4 and 14 previous lines of therapy which in all cases included brentuximab vedotin (Adcetris) and anti-PD1 antibodies. Of note, patient #4 had also previously received a CD30-CAR-T.

Conference Call/Webcast Details

Affimed will host a conference call and webcast on April 14, 2021, at 4:05 p.m. EDT to discuss the initial study findings. The conference call will be available via phone and webcast. To access the call, please dial +1 (646) 741-3167 for U.S. callers, or +44 (0) 2071 928338 for international callers, and reference passcode 1788338 approximately 15 minutes prior to the call.

A live audio webcast of the conference call will be available in the "Webcasts" section on the "Investors" page of the Affimed website at View Source A replay of the webcast will be accessible at the same link for 30 days following the call.

About the Phase 1 Study

The University of Texas MD Anderson Cancer Center is studying AFM13 in an investigator-sponsored Phase 1 trial in combination with cord blood-derived allogeneic NK cells in patients with recurrent or refractory CD30-positive lymphomas. The study is a dose-escalation trial of pre-complexed NK cells, with patients receiving 1×106 NK cells/kg in Cohort 1; 1×107 NK cells/kg in Cohort 2; and, 1×108 NK cells/kg in Cohort 3. The trial is designed to explore safety and activity and determine the recommended Phase 2 dose. In each cohort, the dose of the pre-complexed NK cells with AFM13 is to be followed by weekly doses of 200 mg AFM13 monotherapy for three weeks, with each patient evaluated for dose-limiting toxicities and responses on day 28.

MD Anderson has an institutional financial conflict of interest with Affimed related to this research and has therefore implemented an Institutional Conflict of Interest Management and Monitoring Plan.

Additional information about the study can be found at www.clinicaltrials.gov (NCT04074746).

About AFM13

AFM13 is a first-in-class innate cell engager (ICE) that uniquely activates the innate immune system to destroy CD30-positive hematologic tumors. AFM13 induces specific and selective killing of CD30-positive tumor cells, leveraging the power of the innate immune system by engaging and activating natural killer (NK) cells and macrophages. AFM13 is Affimed’s most advanced ICE clinical program and is currently being evaluated as a monotherapy in a registration-directed trial in patients with relapsed/refractory peripheral T-cell lymphoma or transformed mycosis fungoides (REDIRECT). The study is actively recruiting, and additional details can be found at www.clinicaltrials.gov (NCT04101331).