On July 15, 2019 Neon Therapeutics, Inc. (Nasdaq: NTGN), a clinical-stage immuno-oncology company developing neoantigen-based therapeutics, reported top-line results, with at least 12-month median follow-up, from the ongoing, multicenter Phase 1b clinical trial evaluating NEO-PV-01, Neon’s personal neoantigen vaccine candidate, in combination with OPDIVO in patients with advanced or metastatic melanoma, smoking-associated non-small cell lung cancer (NSCLC) and bladder cancer (Press release, Neon Therapeutics, JUL 15, 2019, View Source [SID1234537527]). Across all three distinct tumor types, results demonstrated prolonged and consistent improvements in progression-free survival (PFS) that compare favorably to that observed with checkpoint inhibitor monotherapy, based on historical benchmark data. At 13.4-month median follow-up in 34 patients with metastatic melanoma, median PFS had not yet been reached. In 27 patients with metastatic NSCLC, median PFS was 5.6 months; and in 21 patients with metastatic bladder cancer, median PFS was 5.6 months. These top-line data, which come from 82 patients who received at least one dose of OPDIVO in the Phase 1b NT-001 trial (Intention-to-Treat analysis, or ITT), support further development of NEO-PV-01, including randomized Phase 2 trials of NEO-PV-01 in metastatic disease settings. The NT-001 trial was initiated in November 2016 and completed enrollment in July 2018.

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!

"Collectively, these data demonstrate a promising new approach in the field of cancer immunotherapy with the potential to further broaden and extend the benefits of checkpoint inhibitor treatment to improve patient outcomes in multiple cancer settings. Monotherapy checkpoint inhibitors have historically shown a range in median progression-free survival in metastatic melanoma, non-small cell lung and bladder cancers of approximately 3-7 months, 2-4 months and 2-3 months, respectively. With these NT-001 results, we are observing consistent prolongation of progression-free survival across all three tumor types compared with historical checkpoint inhibitor monotherapy studies involving patients with similar baseline characteristics. This is an exciting step in establishing the potential of neoantigen-based therapies as a vital component of the cancer treatment landscape," said Patrick Ott, M.D. Ph.D., Clinical Director, Melanoma Center, Center for Immuno-Oncology at the Dana-Farber Cancer Institute and a lead investigator in the NT-001 trial. "Importantly, these clinical outcome improvements, when coupled with the immune and pathological changes seen after vaccination that were presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) 2019 Annual Meeting, are consistent with the mechanism of action of NEO-PV-01."

NT-001 Clinical Trial Top-Line Results1
ITT analysis includes 82 patients receiving at least one dose of OPDIVO (as of April 2019 data cut)

Metastatic Melanoma
(N=34)
Metastatic Non-Small Cell Lung Cancer
(N=27)
Metastatic Bladder
Cancer
(N=21)
Median Follow-up (months)
13.4
12.0
14.7
Median PFS (months)
Not Yet Reached
(12-Month PFS = 56%)
5.6
5.6
Objective Response Rate
47%
22%
24%
Prior therapy %
41%
67%
71%
1 Please see accompanying presentation at View Source for additional details

As previously presented at the AACR (Free AACR Whitepaper) 2019 Annual Meeting, in data available from the melanoma cohort from an August 2018 data cut, evidence of patients experiencing immune pressure on their tumors in the form of both cascading immune response (epitope spread) and decreased tumor cellularity (biopsies obtained following vaccine treatment) was observed in a majority of patients in the trial who had not progressed at nine months. This evidence of complete histological response of biopsied tumor is a potential correlate for durable clinical benefit and suggests that traditional radiographic analyses may underrepresent the effect that a neoantigen vaccine may have on tumor killing.

"By targeting neoantigens that are specific to each patient’s tumor, we believe that our NEO-PV-01 personal cancer vaccine candidate is helping direct a patient’s immune system to these new cancer targets, which can lead to prolonged clinical benefit. Consequently, we believe that the evidence we are seeing in this clinical trial of broadened neoantigen immune response, epitope spread and histological response suggest that NEO-PV-01 may play an important role in prolonging clinical benefit in combination with checkpoint inhibition, as evidenced by the extended PFS reported in this trial," said Richard Gaynor, M.D., Neon’s President of Research and Development.

The safety data for NT-001 were consistent with the safety profile for OPDIVO monotherapy. In the 60 patients who had received at least one vaccine dose, no serious adverse events were observed that were related to the NEO-PV-01/OPDIVO combination. Low grade adverse events attributable to the NEO-PV-01/OPDIVO combination included injection site reactions, fatigue and influenza-like illness.

"Our NT-001 trial is the first demonstration of improved clinical outcomes for this new class of personal neoantigen therapies in metastatic cancer. We believe Neon is pioneering this exciting new potential approach to treating cancer. The dataset we are presenting today represents an important milestone for Neon and the entire neoantigen field. We believe these data further validate our neoantigen-based platform, including our class-leading RECON bioinformatics platform, and position us well to initiate Phase 2 development of NEO-PV-01 and advance our personal T cell therapy into the clinic," said Hugh O’Dowd, Neon’s Chief Executive Officer.

Continued Development of NEO-PV-01

These top-line results support further development of NEO-PV-01, including randomized Phase 2 trials of NEO-PV-01 in metastatic disease settings. Neon plans to present more detailed data from its NT-001 clinical trial at an upcoming medical society meeting.

Melanoma: Neon plans to initiate a randomized Phase 2 clinical trial in combination with checkpoint inhibitor therapy in a biomarker-defined population of first-line metastatic melanoma patients in 2020. Data analysis from the NT-001 trial is ongoing and will further inform potential biomarker selection. In addition, Neon is conducting its NT-003 trial to evaluate NEO-PV-01 and OPDIVO in combination with other agents, including a CD40 agonist or a CTLA-4 antagonist, to potentially further enhance NEO-PV-01-induced neoantigen immune response and improve clinical outcomes. Neon plans to present immune monitoring data from this trial in the second half of 2020.

NSCLC and Bladder Cancer: Neon also believes that the NT-001 results in advanced or metastatic NSCLC and bladder cancers support continued development of NEO-PV-01 in these settings. The NT-001 data provide increased confidence in NEO-PV-01’s potential to improve clinical benefit in combination with standard of care, such as with checkpoint inhibitor therapy and chemotherapy, for these difficult to treat cancers. As announced in April 2019, Neon has completed enrollment in NT-002, its Phase 1b clinical trial evaluating NEO-PV-01 in combination with the current standard of care, KEYTRUDA (pembrolizumab) and chemotherapy, in first-line patients with untreated advanced or metastatic NSCLC. Neon expects to

report immune monitoring and clinical outcome data from this trial by the end of the third quarter of 2020, which will inform future randomized clinical trials.

OPDIVO is a registered trademark of Bristol-Myers Squibb Company. KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Conference Call Information

Neon will host a conference call and webcast today at 8:30 A.M. ET to discuss the top-line results from its Phase 1b NT-001 clinical trial. The live webcast can be accessed on the investor page of Neon’s website at View Source. The conference call can be accessed by dialing (866) 353-0265 and using the conference ID 5596197. A replay of the webcast will be available on Neon’s website approximately two hours after the completion of the event and will be archived for up to 30 days.

About NEO-PV-01

NEO-PV-01 is Neon’s investigational personal neoantigen vaccine, which is custom-designed and manufactured based on the unique mutational fingerprint of each individual patient. NEO-PV-01, which is designed to include up to 20 neoantigen-targeting peptides selected by Neon’s RECON bioinformatics engine, is intended to generate an anti-tumor immune response directing T cells to target particular neoantigens in the patient’s tumor. NEO-PV-01 is being studied in multiple ongoing Phase 1 clinical trials.

About Neon’s NT-001 Clinical Trial

NT-001 is a Phase 1b clinical trial evaluating Neon’s investigational personal neoantigen vaccine, NEO-PV-01, in combination with OPDIVO (nivolumab) in checkpoint-naïve patients with metastatic melanoma, smoking-associated NSCLC or bladder cancer. OPDIVO is a PD-1 immune checkpoint inhibitor designed to overcome immune suppression. Neon’s NT-001 trial is intended to evaluate the combination of NEO-PV-01 with OPDIVO and the potential to broaden a patient’s anti-tumor immune response, resulting in improved duration of clinical benefit. The NT-001 trial is being conducted at nine leading U.S. cancer centers and includes first-, second- and later-line metastatic patients who were eligible to participate if they had received no more than one prior systemic treatment. The primary endpoint of the trial is to evaluate the safety of NEO-PV-01 in combination with OPDIVO and secondary endpoints include the clinical efficacy of the combination over two years of follow-up. Exploratory endpoints include correlative immune response with clinical outcome endpoints.

On July 15, 2019 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) reported that plans to report second quarter 2019 financial results on July 30, 2019. Ligand’s CEO John Higgins, President and COO Matt Foehr, and Executive Vice President and CFO Matt Korenberg will host the conference call (Press release, Ligand, JUL 15, 2019, View Source [SID1234537525]).

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!

Second Quarter 2019 Earnings Call

What:

Ligand conference call to discuss financial results and provide general business updates

When:

Tuesday, July 30, 2019

Time:

9:00 a.m. Eastern time (6:00 a.m. Pacific time)

Conference Call:

(833) 591-4752 within the U.S.

(720) 405-1612 outside the U.S.

Conference ID – 1997313

Webcast:

Live conference call webcast and replay accessible at www.ligand.com

On July 15, 2019 Boehringer Ingelheim reported its acquisition of all shares of AMAL Therapeutics SA, a private Swiss biotechnology company focused on cancer immunotherapy and advancing first-in-class therapeutic cancer vaccines derived from its technology platform KISIMA (Press release, Boehringer Ingelheim, JUL 15, 2019, View Source [SID1234537524]). AMAL’s lead vaccine ATP128 is currently developed for stage IV colorectal cancer and is slated to begin first-in-human trials later this month. Boehringer Ingelheim plans to develop new therapies by combining assets from its cancer immunology portfolio with AMAL’s proprietary KISIMA immunization platform.

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!

Michel Pairet
"Acquiring AMAL is part of Boehringer Ingelheim’s long-term strategy to enhance our existing position as an innovator of novel cancer therapies, including immuno-oncology treatments, which leverage cutting-edge scientific discoveries and their applications," said Michel Pairet, member of Boehringer Ingelheim’s Board of Managing Directors with responsibility for the company’s Innovation Unit. "We want to pioneer new paradigms of biology-based care for cancer patients, and the technologies and expertise developed at AMAL are critical to our efforts."

The total transaction could amount up to EUR 325 million, and is comprised of an upfront payment as well as contingent clinical, development and regulatory milestones plus up to EUR 100 million if certain commercial milestones are hit.

"I am extremely proud of the hard work of AMAL’s entire team, which is validated by this acquisition, and very excited to further develop the KISIMA technology platform within Boehringer Ingelheim," said Madiha Derouazi, Ph.D., Founder and Chief Executive Officer of AMAL Therapeutics. "Our new relationship with Boehringer Ingelheim will enable us to realize the full potential of our KISIMA platform to fight solid cancers while preserving AMAL’s approach to biotechnology research and our scientific and academic networks. Moreover, sharing resources and capabilities in clinical development will greatly help us to move ATP128 and other assets forward."

Boehringer Ingelheim’s Cancer Immunology group is built to discover therapies that engage triggering of immune responses against non-inflamed, "cold" tumors, which represent a large group of cancer types refractory to many treatments, including checkpoint inhibitor drugs. Immune targeting of cold tumors is a particular challenge. AMAL’s KISIMA vaccine technology, designed to stimulate potent immune responses, is a promising therapeutic option for patients with these type of cancers.

The AMAL acquisition, along with that of the 2018 acquisition of Vira Therapeutics (Vira-T) and in-license of OSE Immunotherapeutics’ SIRP-alpha targeting antibody, significantly strengthens Boehringer Ingelheim’s strategic focus on immune cell-directed therapies. By combining its world-class in-house research and development with that of highly innovative biotechnology companies, Boehringer Ingelheim is developing innovative immuno-oncology therapies and accelerating the delivery of the next-generation of cancer treatments.

AMAL is headquartered on the medical campus of the University of Geneva, from which it was spun-out in 2012, with financial backing from a syndicate of both corporate and institutional investors, including the Boehringer Ingelheim Venture Fund and High-Tech Gründerfonds as the initial seed investors. Additional investments were provided by VI Partners, Helsinn Investment Fund, BioMed Partners and Schroder Adveq. AMAL’s technology platform and derived products are protected by a broad portfolio of patents and licenses.

KISIMA
Unlike prophylactic vaccines that immunize a patient to prevent an infection before it occurs, therapeutic vaccines combat existing diseases. Anti-cancer therapeutic vaccines carry antigens, pieces of protein that also are in tumors. By presenting antigens to the patient’s immune system, a vaccine can prompt tailor-made responses, including activation of killer T cells that target the tumor and can boost memory immunity to reduce the risk of relapse.

AMAL’s proprietary technology platform KISIMA enables the assembly of three functional components into one patented fusion protein used as a vaccine: First, a proprietary cell-penetrating peptide for antigen delivery; second, a proprietary toll-like receptor (TLR) peptide agonist as an adjuvant, and third, a multi-antigenic cargo that can be tailored for specific indications.

ATP128
AMAL’s lead candidate, ATP128, is a therapeutic chimeric recombinant protein vaccine designed using KISIMA and currently developed for stage IV colorectal cancer. AMAL will conduct KISIMA-01, an international Phase Ib clinical study to evaluate the combination of ATP128 with Boehringer Ingelheim’s anti-PD1 compound BI754091, via a May 2019 collaborative agreement, in Microsatellite Stable (MSS) patients with stage IV colorectal cancer.

This first-in-human study will investigate ATP128 as single agent and in combination with BI754091 using safety and tolerability as primary endpoints. The study will also measure anti-tumor activity and characteristics of the immune response as secondary and exploratory endpoints.

On July 15, 2019 Advaxis, Inc. (NASDAQ: ADXS), a clinical-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, reported new immune data from its ongoing ADXS-NEO Phase 1 clinical trial that further support the clinical potential for the company’s platform in neoantigen-directed immunotherapies (Press release, Advaxis, JUL 15, 2019, View Source [SID1234537523]).

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!

ADXS-NEO is a personalized immunotherapy that is designed to help a patient’s immune system recognize and respond to mutation-derived tumor antigens, or neoantigens, that are unique to his or her tumor. ADXS-NEO is designed to express tLLO fused to up to 40 patient-specific neoantigens arranged sequentially as beads-on-a-string. As a live attenuated bacterial vector, ADXS-NEO can be rapidly taken up by antigen presenting cells, which recognize it as foreign and present the tLLO-NEO fusion proteins to T cells by the major histocompatibility complex class I and II pathways.

ADXS-NEO is being evaluated in an open-label, dose-escalation, multicenter Phase 1 clinical trial in the United States. Part A of the study is open to patients with metastatic non-small cell lung cancer (NSCLC), metastatic microsatellite stable colorectal cancer (MSS-CRC) and metastatic squamous cell carcinoma of the head and neck (SCCHN) who will receive ADXS-NEO as monotherapy. Part B of the study, anticipated to begin later this year, will be open to NSCLC patients as well as patients with melanoma SCCHN and bladder cancer and, for this part, ADXS-NEO will be administered in combination with a checkpoint inhibitor.

The new data were derived from deconvolution of neoantigen pools using single peptides and in vitro stimulation ELISpot assays (minimal CD8+ peptides). This has now been completed for the first two patients enrolled in this study, one with NSCLC and one with MSS-CRC. Highlights of the new post-vaccination data with ADXS-NEO are as follows:

CD8+ T cells were generated against 90% of the 40 neoantigen targets contained in the drug construct for the MSS-CRC patient (the NSCLC patient did not have 40 neoantigen targets and there were certain other issues with this patient’s sample that, together, made it unsuitable for inclusion in this "hit rate" analysis). This is consistent with Advaxis’ previously reported data from its preclinical studies as well as from clinical studies using pooled neoantigen peptides which were presented at the American Association of Cancer Research Annual Meeting last year and earlier this year, respectively. This is the highest "hit rate" publicly reported to-date in the neoantigen field. This high "hit rate", along with the rapid immune responses seen and antigen spreading, lay the foundation for the ADSX-NEO platform to be best-in-class for personalized, neoantigen-directed immunotherapies.

CD8+ T cells were also generated against the hotspot mutations found within each of the two patients’ tumors (i.e., EGFRL858R in the NSCLC patient and KRAS G12A in the MSS-CRC patient). This is important for the ADXS-NEO program as Advaxis believes a number of patient tumors likely will present with hotspot mutations, and generating or maintaining CD8+ T cell activity against these targets may increase the potential for killing cancer cells. All of the first four patients in this Phase 1 trial had a hotspot mutation. This is also relevant for the company’s ADXS-HOT program in that this is the first time Advaxis has observed the ability to generate or maintain specific CD8+ T cell activity against hotspot mutations. Hotspot mutations are important targets contained within the numerous drug constructs within the ADXS-HOT program and the specific hotspot mutations in these two patients, EGFRL858R and KRAS G12A, are included in the company’s ADXS-503 (HOT Lung) and ADXS-508 (HOT Colorectal) drug constructs, respectively.

Antigen spreading was confirmed in the MSS-CRC patient showing specific CD8+ T cells against neoepitopes that were not contained in the drug construct prepared for this patient (the NSCLC patient’s sample was not re-tested for antigen spreading). Thus, Advaxis believes ADXS-NEO may be able to induce a specific immune response against neoantigen-bearing tumor cells with the resultant cell death releasing secondary (nontargeted) tumor antigens. These secondary antigens can then prime subsequent immune responses (antigen spread) that are thought to be responsible for the improved clinical outcomes documented with other immunotherapies. Of note, antigen spreading has also been induced with other Lm constructs such as ADXS-HPV and ADXS-PSA in cervical and prostate cancer patients, respectively.

To date, dosing of ADXS-NEO at 1×108 colony forming units (CFU) has been well-tolerated in two patients. ADXS-NEO dosed at 1×109 CFU was beyond the maximum tolerated dose with reversible Grade 3 hypoxia (n=2) and Grade 3 hypotension (n=1) dose-limiting toxicities.

"This preliminary dataset of the deconvolution assays shows the generation of specific CD8+ T cell response in one MSS-CRC patient against 90% of the neoantigens in that patient’s personalized Lm construct together with antigen spreading, both of which we believe are critical for potential clinical benefit. These encouraging results are consistent with data from our previous preclinical and ELISpot-pooled clinical studies, and we look forward to presenting data from all patients in the monotherapy arm later in the year," said Andres Gutierrez, M.D., Ph.D., Chief Medical Officer of Advaxis. "In addition, we are gaining valuable insight from our ADXS-NEO platform to help advance our ADSX-HOT drug constructs, as for the first time we observed the ability to generate specific CD8+ T cell activity against hotspot mutations in the clinic. We continue to enroll patients in this Phase 1 study for ADXS-NEO and look forward to starting Part B with ADXS-NEO in combination with a checkpoint inhibitor later this year."

On July 15, 2019 AbbVie (NYSE: ABBV) reported that it has acquired Seattle-based Mavupharma, a privately held biopharmaceutical company focused on novel approaches to target the STING (STimulator of INterferon Genes) pathway for the treatment of cancer (Press release, AbbVie, JUL 15, 2019, View Source [SID1234537522]).

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!

STING pathway signaling plays an important role in the generation of an immune response directed at tumors, and enhancing STING signaling has shown promise in a variety of tumor models. STING pathway stimulation has the potential to increase the susceptibility of tumors and broaden treatment options for patients.

"AbbVie’s vision in oncology is to advance breakthrough areas of science leading to a strong pipeline of innovative cancer therapies," said Steve Davidsen, Ph.D., vice president of oncology discovery, AbbVie. "Mavupharma’s platform has the potential to further our immuno-oncology portfolio and assist in the development of transformative medicines for patients."

Mavupharma’s lead clinical candidate is MAVU-104, a first-in-class, orally active, small molecule inhibitor of ENPP1, an enzyme involved in the regulation of the STING pathway. Inhibiting ENPP1 activity with MAVU-104 allows for highly controlled enhancement of STING signaling in tumors without the need for injections.

"AbbVie has built a leadership position in oncology and their world-class capabilities will enable the accelerated development of our pipeline of STING modulators," said Michael Gallatin, Ph.D., former president and a co-founder of Mavupharma.

"We made tremendous strides in developing our novel STING modulators and advancing MAVU-104 towards the clinic. We are confident in AbbVie’s ability to continue to advance this exciting science for patients," added former chief scientific officer and co-founder Gregory Dietsch, Ph.D.

Financial terms of the transaction were not disclosed.