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Sensei Biotherapeutics Presents Clinical Trial Data Demonstrating SNS-301 Induces Rapid and Robust Antigen-specific Immune Responses at the Society for Immunotherapy of Cancer’s 33rd Annual Meeting

On November 6, 2018 Sensei Biotherapeutics, Inc., a clinical-stage biopharmaceutical company developing precision immuno-oncology therapies, reported that clinical and immunological data from the Phase 1 clinical trial of SNS-301 will be highlighted in a poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 33rd Annual Meeting, to be held November 9-11, 2018 in Washington, D.C (Press release, Sensei Biotherapeutics, NOV 6, 2018, View Source [SID1234530933]). Data showed rapid and significant antigen-specific B-cell and T-cell responses induced by SNS-301, a first-in-class cancer immunotherapy targeting human aspartate β-hydroxylase (ASPH), a novel tumor-specific embryonic antigen.

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"These data clinically confirm the immunogenicity and mechanism of action of SNS-301, as we see strong, ASPH-targeted activation of the immune system in patients who received the immunotherapy. Taken together, the data indicate that SNS-301 is capable of overcoming central immune tolerance. We plan to target ASPH with both cancer vaccines and cell therapies to benefit different patient populations," said John Celebi, President and Chief Executive Officer of Sensei Biotherapeutics. "Based on these encouraging results, we look forward to initiating a Phase 2 trial for SNS-301 in various hematological malignancies and solid tumors in early 2019."

Twelve patients with biochemically recurrent prostate cancer who were screened for ASPH using Sensei’s proprietary companion diagnostic were treated with SNS-301 in the Phase 1, multi-center, proof-of-concept study. SNS-301 was administered every 21 days via intradermal injection using a fixed dose-escalation schema through which patients received between 8 and 23 doses at three different dose ranges, and the recommended Phase 2 dose was determined based on the immunogenicity data and changes seen in prostate specific antigen (PSA) doubling times at the three evaluated doses. Highlights of the immunogenicity data from the SNS-301 Phase 1 study presented at SITC (Free SITC Whitepaper) include:

Natural Killer (NK) cell levels in patients treated with SNS-301 were higher than NK cell levels in healthy donors, indicating activation of the innate immune system.
All patients evaluable for immune profiling experienced dose-dependent, ASPH-specific immune responses including B-cell, T-cell and antibody responses.
Increases in activated interferon gamma (IFN-γ) releasing T cells were demonstrated, and both ASPH-specific CD4+ helper T cells and CD8+ cytotoxic T cells showed dose-dependent activation over the first six cycles of SNS-301 dosing with peak responses often occurring after only three or four doses.
An average of eight to ten-fold increase in the percentage of ASPH-specific CD8+ T cells was observed post-treatment, compared to baseline measurements.
Anti-ASPH antibody titers increased in a dose-dependent manner over the first four to six cycles (80-120 days) after administration of SNS-301. This increase in antibody response correlated with concomitant increases in the percentages of ASPH-specific B cells, as measured by flow cytometry.
An average five to seven-fold increase in the percentage of ASPH-specific B-cell responses was observed post-treatment, compared to baseline measurements.
Eight out of the twelve patients (67%) achieved improvements in PSA doubling time and/or absolute PSA level, leading to decreased PSA velocity and suggesting a disease stabilizing effect of SNS301.
Based on evaluation of the three different dose ranges (2 x 1010, 1 x 1011, 3 x 1011 particles), immune responses occurred more rapidly at the two higher doses, as compared to the lower dose. Immunologic efficacy generally correlated with biochemical responses in these patients.
In the Phase 1 study, SNS301 was well tolerated with a favorable safety profile at all three dose levels with no dose-limiting toxicities or grade 4 or 5 adverse events.

About SNS-301
SNS-301 is a first-in-class cancer immunotherapy targeting human aspartate β-hydroxylase (ASPH), a cell surface enzyme that is normally expressed during embryonic development. Following embryonic development, the protein is no longer expressed in healthy adults. Expression of ASPH is uniquely upregulated in more than 20 different types of cancer and is related to cancer cell growth, cell motility and invasiveness. ASPH alters signaling that occurs through the Notch pathway and its expression levels in various tumors are inversely correlated with disease prognosis. SNS-301 is a bio-engineered, inactivated bacteriophage virus expressing a fusion protein of native bacteriophage gpD (gene product D) and a selected domain of ASPH. SNS-301 is designed to overcome immune tolerance and induce robust and durable ASPH-specific humoral and cellular responses. SNS-301 is paired with a companion diagnostic to ensure appropriate patient selection and is delivered easily through an intradermal injection to aid in generating robust immune response.

Atreca to Present Data Further Demonstrating Ability of the Company’s Discovery Engine to Identify Patient-Derived Antibodies that Target Non-Autologous Tumor Tissue

On November 6, 2018 Atreca, Inc., a biotechnology company focused on developing novel therapeutics based on a deep understanding of the human immune response, reported that it will present results from a study that further demonstrates the ability of the Company’s proprietary Discovery Engine, featuring the Company’s Immune Repertoire Capture (IRC) technology, to identify antibodies from treatment-responsive cancer patients that bind to non-autologous tumor tissue (Press release, Atreca, NOV 6, 2018, View Source [SID1234530932]). The study will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 33rd Annual Meeting being held November 7-11, 2018, at the Walter E. Washington Convention Center in Washington, D.C.

"Atreca has built a proprietary and unique discovery platform that enables us to discover, in a very efficient and industrialized manner from active immune responses, antibodies that can serve as the foundation of therapeutics," said Tito A. Serafini, Ph.D., Chief Strategy Officer and an Atreca founder. "The results to be presented at this conference provide another example of what this Discovery Engine enables in oncology; namely, our ability to identify tumor-targeting antibodies in treatment-responsive patients with the potential to be developed into therapeutics designed to treat large patient groups. Our most advanced program, ATRC-101, which we anticipate entering clinical trials in 2019, is a product of this approach."

In the study, (Abstract #O3; Title: Anti-tumor immune responses in metastatic breast cancer exceptional responder patients) to be presented both as an oral presentation and a poster by William Robinson, M.D., Ph.D., Professor of Medicine at Stanford University and an Atreca Founder, Atreca researchers collaborated with researchers led by Joyce O’Shaughnessy, M.D., at Baylor University Medical Center and Texas Oncology. Atreca researchers investigated the properties of antibodies identified in the active immune response of eleven metastatic breast cancer patients who had exceptional and durable responses to systemic therapy. Of the patient-derived antibodies assessed, over 40% displayed specific immunoreactivity to breast carcinoma tissue from unrelated patients, but not to adjacent tissue, indicating that they bind to public tumor antigens. Multiple antibody lineages, predominantly of the IgG2 subclass, showed evidence of convergent antibody evolution across patients, and a subset of responder antibodies drove killing of tumor cells in in vitro functional assays.

Abstract Title: Anti-tumor immune responses in metastatic breast cancer exceptional responder patients (Abstract #O3)

Oral Presentation

Concurrent Session 216: Role of B cells in Immunotherapy & Toxicity
Date & Time: Saturday, Nov. 10, 6:10 – 6:25 p.m. EST
Location: East Salon ABC
Atreca also has a second presentation. Details are below:

Abstract Title: The identification of potent anti-tumor antibodies applicable for ADC therapeutics from patients undergoing immunotherapy (Abstract #P1)

Poster Display (for both posters)

Date & Time: Friday, Nov. 9, from 8 a.m. – 8 p.m. EST and Saturday, Nov. 10, from 8 a.m. – 12 p.m. EST
Presentation Hours: Friday, Nov. 9, 12:45 – 2:15 p.m. EST and 6:30 – 8 p.m. EST
Location: Hall E

Vedanta Biosciences Announces Preclinical Data on Microbiome-Derived Immuno-Oncology Candidate

On November 6, 2018 Vedanta Biosciences, a clinical-stage company developing a new category of therapies for immune-mediated diseases based on rationally-defined consortia of human microbiome-derived bacteria, reported preclinical data for VE800, the Company’s orally-administered, live biotherapeutic product candidate in immuno-oncology (Press release, Vedanta Biosciences, NOV 6, 2018, View Source [SID1234530930]). The study showed that VE800 elicited an anti-tumor immune response as a monotherapy and also enhanced effects of immune checkpoint inhibitors. Additionally, the results describe a mechanism of action for VE800 as the robust interferon-gamma producing CD8+ (cytotoxic) T cell response was elicited via activation of dendritic cells. The data will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 33rd Annual Meeting by Dr. Bruce Roberts, Chief Scientific Officer of Vedanta Biosciences, on November 8. Vedanta Biosciences expects to initiate a clinical study of VE800 in mid-2019.

"Our work shows that VE800 induces robust tumor infiltration by cytotoxic T cells – one of the strongest predictors of response to checkpoint inhibitors – and promotes suppression of tumor growth and enhanced survival in a range of cancer models," said Bruce Roberts, Ph.D., Chief Scientific Officer of Vedanta Biosciences. "To our knowledge, VE800 is the most advanced immuno-oncology product candidate based on a defined consortium of human microbiome-derived bacteria, a therapeutic modality that Vedanta is pioneering. With our cGMP manufacturing processes in place, we’re well-positioned to take VE800 into the clinic in the coming months."

In the preclinical study, VE800 was assessed alone and in combination with various checkpoint inhibitors in colon carcinoma and melanoma tumor models. VE800 was assessed for its ability to induce CD8+ T cells, an important marker of anti-tumor response, as well for its ability to influence accumulation of tumor infiltrating lymphocytes. The study was conducted in collaboration with Dr. Kenya Honda of Keio University, a leader in the microbiome field and a scientific co-founder of Vedanta Biosciences.

Data highlights include:

1. VE800 robustly promoted induction of interferon-gamma producing CD8+ T cells via activation of intestinal dendritic cells and stimulation of interferon-gamma producing CD8+ T cells in a manner dependent on the transcription factor BATF3
2. VE800 enhanced the anti-tumor activity of both anti-PD-1 and anti-CTLA4 antibodies by increasing the level of tumor infiltrating CD8+ T cells
3. VE800 also promoted systemic immune cell activation as evidenced by accumulation of CD8+ T cells in the spleen.

Unlike fecal transplants or single strain approaches to microbiome modulation, Vedanta Biosciences uses pure, clonal cell banks to produce defined collections, or consortia, of bacterial strains designed to effect durable therapeutic changes in a patient’s microbiota. This bypasses the need to rely on direct sourcing of fecal donor material of inconsistent composition.

About VE800
VE800 is Vedanta Biosciences’ oral immuno-oncology product candidate. It consists of a rationally-defined bacterial consortium that activates cytotoxic CD8+ T cells, a type of white blood cell that is the predominant effector in cancer immunotherapy. In preclinical studies, VE800 has been shown to enhance the ability of these T cells to infiltrate tumors, thereby promoting suppression of tumor growth and improving survival. Data also suggest that VE800 may enhance the effects of checkpoint inhibitors. Vedanta Biosciences is evaluating VE800 alone and in combination with checkpoint inhibitors as a potential treatment for patients with advanced or metastatic cancers.

Jnana Therapeutics Announces Appointment of Joanne Kotz, Ph.D. as Chief Executive Officer

On November 6, 2018 Jnana Therapeutics reported that Joanne Kotz, Ph.D., a company co-founder, has been named Chief Executive Officer (Press release, Jnana Therapeutics, NOV 6, 2018, View Source [SID1234530929]). Dr. Kotz has served as Jnana’s president since December 2017.

"Joanne has demonstrated exceptional leadership in guiding the company through its early stages of growth, and we believe she is the ideal person to bring Jnana through its next phase and execute on the company’s vision to unlock SLC transporters as a therapeutic class," said Dr. Amir Nashat, a member of Jnana’s Board of Directors and a managing partner at Polaris Partners. Dr. Nashat also served previously as the company’s interim Chief Executive Officer. "She has built a talented team and a collaborative, empowering culture, while also leading important work to validate Jnana’s proprietary drug discovery platform. Together these position Jnana for even greater success going forward."

Dr. Kotz has broad life sciences experience in research, business, and operations. She helped formulate the initial scientific strategy for Jnana and has led the business and operations of the company since its launch in January 2017. Prior to founding Jnana, she held a leadership position in the F-Prime Biomedical Research Initiative, whose mission is to advance the discovery of novel therapeutic agents for the treatment of neurodegenerative disease by funding early-stage research in academia and biotech companies. Prior to F-Prime, Dr. Kotz was a director at the Broad Institute, where she played a leadership role in creating and guiding partnerships to advance drug discovery efforts, including the Broad-Bayer collaboration in oncology that resulted in the identification of multiple drug candidates. She received a Ph.D. in chemistry from the University of California, Berkeley and conducted postdoctoral research at the Necker Children’s Hospital in Paris and at Genentech.

"I am very proud of what the Jnana team has accomplished to date," said Dr. Kotz. "We have made significant progress in advancing our technology platform, which is the first to explicitly target the SLC family of metabolite transporters, established a strategic collaboration with Neurocrine Biosciences to discover new medicines for central nervous system disorders, and recruited a strong team committed to making a positive impact on patients and their families. I am honored to have been chosen to serve as CEO, and look forward to guiding Jnana’s efforts to transform our knowledge of SLCs into new therapeutics for patients lacking viable treatment options."

CytomX Therapeutics Announces Third Quarter 2018 Financial Results

On Novembber 6, 2018 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a clinical-stage, oncology-focused biopharmaceutical company pioneering a novel class of investigational antibody therapeutics based on its Probody therapeutic technology platform, reported third quarter 2018 financial results (Press release, CytomX Therapeutics, NOV 6, 2018, View Source/news-releases/news-release-details/cytomx-therapeutics-announces-third-quarter-2018-financial" target="_blank" title="View Source/news-releases/news-release-details/cytomx-therapeutics-announces-third-quarter-2018-financial" rel="nofollow">View Source [SID1234530888]).

As of September 30, 2018, CytomX had cash, cash equivalents and short-term investments of $464.6 million.

"During the third quarter, CytomX made broad progress across our highly innovative pipeline of Probody therapeutics," said Sean McCarthy D.Phil., president and chief executive officer. "CX-072, our lead PD-L1 Probody drug candidate, continues to advance in the clinic, as evidenced by our presentations at ESMO (Free ESMO Whitepaper) that reinforce the encouraging safety and clinical activity profiles of CX-072 as both a monotherapy and in combination with ipilimumab. These clinical data also provide further proof-of-concept for our unique platform. During the quarter, we also initiated a clinical trial for CX-2029, a CD71-directed Probody drug conjugate partnered with AbbVie, continued to advance CX-2009, our PDC targeting CD166, and recently filed an IND for CX-188, our Probody therapeutic targeting PD-1. The ongoing translation of our novel science into the clinic is exciting to see."

Business Highlights and Recent Developments

PROCLAIM-CX-072 (PD-L1 Probody Therapeutic) Clinical Program

CX-072 is a potentially best in class Probody therapeutic targeting PD-L1, a clinically- and commercially-validated anti-cancer target.
CytomX presented updated interim clinical data from two arms of the Phase 1/2 PROCLAIM-CX-072 program with a data cutoff of August 3, 2018 at the 2018 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting.
CX-072 monotherapy was studied in PD-L1/PD-1 inhibitor naïve patients with advanced unresectable solid tumors or lymphomas for which no PD-L1 or PD-1 inhibitor was approved or available for their disease (Parts A and A2).
The Maximum Tolerated Dose (MTD) was not reached.
Of the 46 patients treated, Grade 3/4 treatment-related adverse events (TRAE) were reported in five patients (11%) and Grade 3/4 immune-related adverse events (irAEs) were observed in 3 patients (7%).
Of the 18 patients treated at doses of 3 mg/kg or above, 3 (17%) achieved an objective response with 1 confirmed and ongoing partial response (PR) and 2 unconfirmed PRs observed. Stable disease was observed in 8 patients (44%) for an overall Disease Control Rate (DCR) of 61%.
CX-072 in combination with Yervoy (ipilimumab) was studied in patients with advanced unresectable solid tumors or lymphomas for which no PD-L1 or PD-1 inhibitor was approved or available for their disease (Part B).
Of the 20 patients treated, Grade 3/4 TRAEs were reported in four patients (20%) and Grade 3/4 immune-related adverse events (irAEs) were reported in 2 patients (10%).
Of the 14 patients treated with 3 mg/kg of ipilimumab and 0.3 – 10 mg/kg of CX-072, 3 (21%) achieved an objective response with 1 confirmed complete response (CR), and 2 confirmed PRs observed. Stable disease was observed in 21% of patients for an overall DCR of 43%.
CytomX continues to enroll and dose patients in monotherapy expansion cohorts in 8 undisclosed tumor types at the dose of 10mg/kg (Part D). Initial clinical data from Part D is expected in 2019.
CytomX continues to enroll and dose patients in a combination trial of CX-072 plus Zelboraf (vemurafenib) in patients with V600E BRAF-positive melanoma (Part C).
CytomX will be presenting clinical translational data from Part A2 of the CX-072 monotherapy trial later this week as a poster and in a rapid-fire oral presentation at the 33rd Annual Meeting of The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper).
The Company will be hosting an Analyst and Investor event on Saturday, November 10th at SITC (Free SITC Whitepaper) that will be webcast. Webcast details can be found under the Investor and News section of the Company’s website at www.CytomX.com.

PROCLAIM-CX-2009 (CD166 Probody Drug Conjugate) Clinical Program

CX-2009 is a first in class Probody drug conjugate (PDC) that targets CD166, a broadly and highly expressed tumor antigen.
In the second quarter of 2017, CytomX initiated the PROCLAIM-CX-2009 Phase 1/2 clinical program to evaluate the safety and preliminary anti-tumor efficacy of CX-2009.
Part A (monotherapy dose escalation) was initiated at a dose of 0.25 mg/kg with an anticipated top dose of 6 mg/kg. As of November 2, 2018, the enrolling dose level was 10 mg/kg.
Part A2, was initiated in the second quarter of 2018. In Part A2, patients with CD166+++ expressing tumors are enrolled to receive CX-2009 at doses of 4 mg/kg and above already cleared in Part A (6 patients per dosing cohort). Biopsies are mandatory in A2. As of November 2, 2018, patients were being enrolled in a 9 mg/kg dosing cohort.
CytomX anticipates providing a comprehensive update on the CX-2009 program in the first half of 2019 following the substantial completion of Parts A and A2.
CX-2029 (CD71 Probody Drug Conjugate) Clinical Program

CytomX, in collaboration with AbbVie, is advancing CX-2029, a CD71-directed PDC.
CytomX initiated Part A of the PROCLAIM-CX-2029 Phase 1/2 clinical program in July 2018.
CX-188 (PD-1 Probody Therapeutic) Preclinical Program

CytomX filed an Investigational New Drug (IND) application for CX-188 in October and expects to commence dose escalation studies following IND clearance from the U.S. Food and Drug Administration.
Financial Highlights

In July, CytomX completed an underwritten public offering of 5,867,347 common shares which resulted in net proceeds of $134.6 million to CytomX.
Third Quarter 2018 Financial Results
Cash, cash equivalents and short-term investments totaled $464.6 million as of September 30, 2018, compared to $374.1 million as of December 31, 2017.

Revenue was $12.5 million for the three months ended September 30, 2018, compared to $24.1 million for the three months ended September 30, 2017. The decrease was primarily attributable to the recognition during the third quarter of 2017, in full in accordance with ASC 605, of $14.0 million in revenue (net of the associated sublicense fee of $1.0 million) related to the milestone payment from AbbVie after meeting certain milestones required to begin GLP toxicology studies under the collaboration agreement with AbbVie ("AbbVie CD71 Agreement"). This increase was partially offset by an increase in the third quarter of 2018 of $1.5 million in revenue resulting from the change in method of revenue recognition related to the AbbVie CD71 Agreement from straight-line under ASC 605 to percentage-of-completion under ASC 606 and an increase of $1.5 million in revenue related to the Amgen Collaboration and Licensing Agreement ("Amgen Agreement") executed in September 2017.

Research and development expenses decreased by $1.4 million during the three months ended September 30, 2018 compared to the corresponding period in 2017. The decrease was primarily attributed to the recognition, during the third quarter of 2017, of $10.7 million of non-cash in-process research and development expense and $1.2 million of sublicense fee payable to the University of California, Santa Barbara, both as a result of the Amgen Agreement. These amounts were partially offset by increases in the third quarter of 2018 of $3.2 million in personnel-related expenses and other allocated overhead expenses resulting from an increase in headcount, $2.7 million in lab contracts and services expenses primarily related to CX-2009 Phase 1/2 clinical development and $4.0 million in clinical trial expenses primarily related to CX-072, CX-2009 and CX-2029.

General and administrative expenses increased by $1.9 million during the three months ended September 30, 2018 compared to the corresponding period in 2017. This increase was largely attributed to an increase of $2.1 million in personnel related expenses due to increases in headcount.

Conference Call and Webcast Information

CytomX management will host a conference call today at 5:00 p.m. ET. Interested parties may access the live audio webcast of the teleconference through the Investor and News page of CytomX’s website at View Source or by dialing (877) 809-6037 or (615) 247-0221 and using the passcode 9616738. A replay of the webcast will be available on the CytomX website from November 6, 2018 to November 13, 2018.