2018 – Page 229 – 1stOncology™: Cancer Intelligence Service

Sorrento Therapeutics Anti-CEA CAR-T Demonstrates Significant Therapeutic Activity With Increased Overall Survival in Pancreatic Cancer Patients With Liver Metastases

On November 6, 2018 Sorrento Therapeutics, Inc. (NASDAQ: SRNE) ("Sorrento") reported the release of data from a phase 1b clinical trial administering anti-CEA CAR-T by utilizing a unique Pressure-Enabled Drug Delivery (PEDD) manufactured by TriSalus Life Sciences (Press release, Sorrento Therapeutics, NOV 6, 2018, View Source [SID1234532249]). The preliminary data for the Hepatic Immunotherapy for Metastases (HITM-SURE) clinical trial results will be presented in a poster at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, being held November 7-11 in Washington, DC.

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!

Five patients, four pancreatic and one colorectal, with carcinoembryonic antigen–positive (CEA+), unresectable stage IV adenocarcinoma with liver metastases, who had failed one or more lines of systemic chemotherapy, each received three hepatic artery infusions of Sorrento autologous anti-CEA CAR-T cells using the Hepatic Immunotherapy for Metastases (HITM) method. The immunotherapy was delivered by means of PEDD technology, which overpowers the high pressure within solid tumors that limits the reach and efficacy of therapeutic agents.

Two out of the four pancreatic cancer patients had no viable liver metastases by PET scan after treatment. After 12 months, one patient with stage IV pancreatic carcinoma still showed no evidence of liver metastases on PET imaging, and his primary pancreatic tumor was well-controlled. A second patient with stage IV pancreatic cancer also had no evidence of liver metastases six weeks after CAR-T/PEDD infusions. Median overall survival (OS) post-treatment is 8.3 months and the mean OS is 9.8 months to date. No patient suffered any severe adverse event related to the CAR-T infusions.

"PEDD significantly increased CAR-T, more than five-fold, within liver metastases when compared with low-pressure microcatheters, and serum CEA levels declined on-study in all subjects," said Steven Katz, MD, director of the Office of Therapeutic Development at the Roger Williams Medical Center, and the principal investigator of the trial. "These early results suggest we may be able to achieve a therapeutic dose in solid tumors and avoid the severely limiting systemic side effects, such as neurotoxicity and cytokine release syndrome, that are prevalent with conventional systemic CAR-T administration methods. Furthermore, our delivery approach limits the number of circulating CAR-T cells compared to systemic delivery, which has the potential to improve the safety profile of CAR-T therapies for solid tumors in several critical organs."

"With our CD38 and CEA CAR-T programs, we are addressing the challenges of treating both liquid and solid tumors," stated Henry Ji, PhD, President and CEO. "We are scheduled to discuss with the FDA the continued development of this program towards Licensure."

AVID100 Featured in an Invited Oral Presentation at the 9th Annual World ADC Summit

On November 6, 2018 Forbius, a clinical stage company developing biotherapeutics targeting EGFR and TGF-β pathways, reported an invited oral presentation of AVID100 at the 9th Annual World ADC Meeting (Press release, Forbius, NOV 6, 2018, View Source [SID1234531668]). Robert Lutz, Chief Development Officer of Forbius, will give a presentation entitled "Preclinical & Clinical Development of AVID100: An EGFR-Targeting Antibody Drug Conjugate" on November 13, 2018 at 11 AM Pacific Time.

The AVID100 Phase 1 study was completed mid 2018, having enrolled 24 patients, and established a recommended Phase 2 dose (RP2D) of AVID100 of 240 mg/m2 (~6 mg/kg). This is one of the highest RP2Ds reported for maytansinoid payload ADCs (Deslandes, MAbs. 2014 Jul 1;6(4):859–870) and is expected to be in the therapeutically active range based on preclinical efficacy studies. The majority of treatment related adverse events at RP2D were well-tolerated and grade 1 and 2 in severity. Of note, skin-related side-effects, that have been observed previously for therapeutic anti-EGFR antibodies, remained low grade and well tolerated.

AVID100 is currently undergoing Phase 2a clinical trials in EGFR overexpressing tumors to further evaluate safety and efficacy.

About AVID100
AVID100 is a highly potent EGFR-targeting antibody-drug conjugate (ADC) that was engineered to achieve enhanced anti-tumor efficacy without a corresponding increase in toxicity against skin and other EGFR-expressing normal tissues. In preclinical studies, AVID100 demonstrated significant anti-cancer activity, including in EGFR overexpressing tumor models that are resistant to marketed EGFR inhibitors. AVID100 is the only broadly active anti-EGFR ADC in clinical development.

Yuhan signs $1.25 billion licensing deal with Janssen

On November 6, 2018 South Korean pharma company Yuhan Corp (KS: 000100) reported it has licensed out its new clinical-stage lung cancer drug to Janssen Biotech, a unit of US healthcare giant Johnson & Johnson (NYSE: JNJ), in a deal potentially valued at up to $1.25 billion, according to the Korea Herald and other local media (Press release, Genosco, NOV 6, 2018, View Source [SID1234531533]).

11/16/2018 Yuhan signs $1.25 billion licensing deal with Janssen View Source 2/3 Yuhan said it had entered a licensing and cooperation agreement with Janssen to develop lazertinib, a novel clinical-stage therapeutic candidate for the treatment of patients with non-small cell lung cancer (NSCLC).

Following news of the agreement, shares of Yuhan spiked 29.78% to close at 231,000 won on Monday.
Deal includes $50 million upfront payment
Under the terms of the agreement, Yuhan will receive an upfront payment of $50 million and is eligible to receive up to $1.205 billion in potential
development and commercial milestone payments, along with tiered double-digit royalties on future net sales.
"Yuhan is committed to developing lazertinib as an effective treatment option for patients suffering from NSCLC. And Janssen, with strong
scientific expertise in lung cancer and oncology, is the best strategic partner to achieve this mission," said Lee Jung-hee, president and chief
executive of Yuhan, adding: "We are excited to start this collaboration and dive into advancing this treatment regimen with a focus on improving
the lives of people who suffer from lung cancer."
The compound is currently in an ongoing Phase I/II clinical trials in Korea. Interim results showed that lazertinib exhibited robust disease activity
in patients with NSCLC with acquired resistance to EGFR-TKIs, with or without brain metastasis and was well tolerated with low rates of Grade 3
or higher adverse events.
In 2015, US firm Genosco partnered globally with Yuhan for development and commercialization of lazertinib, on which data from a Phase I/II
study in NSCLC were presented at the annual American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) meeting in June this year.
Results from the open-label, multi-center dose-escalation, Phase I/II study of lazertinib (YH25448, GNS-1480) for patients with advanced EGFRTKI-resistant
NSCLC with or without CNS metastasis concluded that lazertinib was well-tolerated with low rates of Grade 3 or higher adverse
events (AE) and exhibited robust activity in patients with NSCLC with acquired resistance to EGFR-TKIs, with or without brain metastasis.

Arcus Biosciences Announces Third Quarter 2018 Financial Results and Recent Corporate Updates

On November 6, 2018 Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage biopharmaceutical company focused on creating innovative cancer immunotherapies, reported financial results for the third quarter ended September 30, 2018 and provided updates on its clinical and preclinical programs (Press release, Arcus Biosciences, NOV 6, 2018, View Source [SID1234531019]).

"This was another productive quarter for Arcus as we began dosing patients with our third product candidate, AB154, and made significant progress advancing our initial combination trials for AB928," said Terry Rosen, Ph.D., Chief Executive Officer at Arcus. "The starting dose for the dose-escalation portion of our AB928 combination trials is 75 mg once-daily, a dose that demonstrated significant inhibition of the adenosine 2a receptor pathway in our healthy volunteer study. We have incorporated extensive biomarker analysis into the design of our AB928 combination trials to determine if clinical responses observed in the trials can be attributed to the mechanism of action of AB928. We look forward to reporting initial clinical data for both AB928 and AB154, as well as data from our healthy volunteer study of AB680, our small-molecule CD73 inhibitor, in 2019."

Pipeline Updates and Poster Presentations

AB928 (dual A2aR/A2bR antagonist)

Initiated the first three AB928 combination trials in patients. AB928 is being evaluated in combination with other agents in the following Phase 1/1b dose-escalation trials, which are now enrolling patients:

AB928 in combination with Doxil in triple negative breast (TNBC) and ovarian cancers

AB928 in combination with mFOLFOX in colorectal and gastroesophageal cancers

AB928 in combination with AB122, the Company’s anti-PD-1 antibody, in advanced solid tumor types

The Company also expects the following AB928 dose-escalation trial to be open for enrollment shortly:

AB928 in combination with carboplatin/pemetrexed and pembrolizumab in non-small cell lung cancer (NSCLC)

In the above NSCLC trial, the Company also plans to explore AB928 combinations in the relapsed/refractory setting, including in patients previously treated with anti-PD-1 therapy.

Six posters to be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2018 Annual Meeting taking place November 7th through 11th:

"Development of biomarkers to assess adenosine generation & activity in support of clinical trials conducted with the adenosine receptor antagonist AB928" will highlight the development of biomarkers to enable the selection of patients and tumor types with the highest levels of CD73, the rate-limiting enzyme responsible for the production of adenosine.

"Selection of optimized drug candidates, dosing regimen, pharmacodynamic endpoints, tumor types, and biomarkers for translating inhibition of the adenosine pathway into effective anti-tumor activity" will highlight the Company’s strategy for identifying the optimal tumor types to target for each of AB928 and AB680.

Four "Trial in Progress" poster presentations will summarize the design of the Company’s four AB928 combination trials.

Presented final results from the Phase 1 double-blinded, randomized, placebo-controlled trial of AB928 in healthy volunteers in a poster presentation at ESMO (Free ESMO Whitepaper) in October. Data presented in this poster presentation support the selection of the starting dose of AB928 for clinical trials in patients.

Presented a poster on the ability of AB928 to relieve adenosine-mediated immune suppression at the Fourth AACR (Free AACR Whitepaper) International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) in September. The in vitro data presented demonstrate that AB928 prevents adenosine-mediated gene expression changes and suppression of immune cell function and suppresses tumor growth in syngeneic mouse models when administered as a monotherapy or in combination with anti-PD-1 or chemotherapy.

AB122 (anti-PD-1 antibody)

Two posters to be presented at the SITC (Free SITC Whitepaper) 2018 Annual Meeting in November:

"Preliminary results from an ongoing Phase 1 study of AB122 in patients with advanced solid tumors" will include pharmacokinetic, receptor occupancy, safety and clinical activity data from the Phase 1 dose-escalation trial for AB122.

"Development of a robust, simplified method to measure receptor occupancy in peripheral blood from patients treated with a novel anti-PD-1 agent, AB122" will demonstrate, together with the previous poster, that AB122 achieved significant inhibition of PD-1 in patients treated in the first two dosing cohorts of the Phase 1 dose-escalation trial.

Continued dosing patients in the Company’s Phase 1 dose-escalation trial for AB122. As of November 3, 2018, the Company had dosed 20 patients with AB122 evaluating different doses and dosing schedules. Based on data generated to date, the Company selected 240 mg as the dose for the Q2W (every 2 weeks) regimen for AB122.

AB154 (anti-TIGIT antibody)

Dosed the first cohort of patients in the dose-escalation portion of the ongoing Phase 1 trial for AB154 in Australia. This Phase 1 trial is evaluating AB154 in selected solid tumor types. The dose-escalation portion will be followed by the initiation of expansion cohorts in tumor types associated with high levels of TIGIT and/or CD155, the ligand for TIGIT, once the recommended doses for

AB154 as a monotherapy and in combination with AB122 have been identified. The Company plans to file an Investigational New Drug (IND) Application for AB154 in the U.S. by the end of the first quarter of 2019.

Presented a poster on the preclinical characterization of AB154 at the Fourth AACR (Free AACR Whitepaper) International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) in September. Data presented demonstrated that AB154 enhances the T cell activation effects of our anti-PD-1 antibody (AB122) in a mixed lymphocyte assay and that AB154 has sub-nanomolar potency on peripheral blood lymphocytes derived from both healthy donors and NSCLC patients.

Presented a poster at the SITC (Free SITC Whitepaper) 2018 Annual Meeting in November:

"Preclinical characterization of AB154, a fully humanized α-TIGIT antibody, for use in combination therapies" will highlight the Company’s development of a TIGIT occupancy assay, which is being implemented in the ongoing Phase 1 trial of AB154.

AB680 (small molecule CD73 inhibitor)

Received regulatory approval in Australia to initiate a healthy volunteer trial for AB680 (IV formulation). This trial is primarily designed to determine the safety, tolerability and pharmacokinetic profile of AB680 prior to initiating clinical testing of AB680 in cancer patients and is expected to begin dosing shortly. Preclinical data suggest that the half-life of AB680 should be sufficient for clinical dosing every two or three weeks.

Presented a poster on the preclinical pharmacokinetic and pharmacodynamic characterization of AB680 at the Fourth AACR (Free AACR Whitepaper) International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) in September. Data presented demonstrated that AB680 is a highly potent and selective small-molecule inhibitor of CD73 and that AB680 has a long projected human half-life.

IND-enabling studies for an oral formulation of AB680 are ongoing.

Corporate Updates

In October, Arcus announced that Kristin M. Hege, M.D., was appointed to its Board of Directors. Dr. Hege currently serves as Corporate Vice President, Translational Development, Hematology and Oncology and San Francisco site head at Celgene.

Upcoming Milestones

In the first half of 2019, the Company expects to:

Present initial data from the dose-escalation portion of the AB928 Phase 1/1b combination trials, which will include data on safety, biomarker analysis and clinical activity for the combinations, in the second quarter.

Initiate an expansion cohort to evaluate AB122 as a monotherapy to confirm that the activity of AB122 is similar to that of the approved anti-PD-1 antibodies.

Report safety and pharmacokinetic data from the Phase 1 trial of AB680 in healthy volunteers, and initiate the Phase 1 clinical program for AB680 in cancer patients.

In the middle of 2019, the Company expects to:

Initiate the first of the expansion cohorts for the AB928 combination trials.

In the second half of 2019, the Company expects to:

Present additional data from the dose-escalation portion of the AB928 Phase 1/1b combination trials.

Present initial data from the ongoing Phase 1 trial of AB154.

Third Quarter and Year-to-Date 2018 Financial Results

Cash Position: At September 30, 2018, cash and investments (which include cash equivalents and both short-term and long-term investments) were $265.6 million, compared to $175.7 million at December 31, 2017. The increase was primarily due to $124.7 million in net proceeds from the Company’s initial public offering in March.

Revenues: Collaboration and license revenues for the third quarter ended September 30, 2018 were $4.3 million, compared to $0.2 million for the same period in 2017. Collaboration and license revenues for the nine months ended September 30, 2018 were $6.8 million, compared to $0.2 million for the same period in 2017. The increase in revenues for both periods was attributable to revenues recognized from the Option and License Agreement the Company entered into with Taiho Pharmaceutical Co., Ltd in September 2017.

R&D Expenses: Research and development expenses for the third quarter ended September 30, 2018 were $12.9 million, compared to $21.4 million for the same period in 2017. The decrease was due to licensing costs of $15.0 million paid to WuXi Biologics in the third quarter ended September 30, 2017, partially offset by an increase in clinical and manufacturing costs related to the Company’s initiation of its AB928 combination and AB154 clinical trials, preclinical and manufacturing costs to prepare AB680 for clinical trials, an increase in R&D headcount to support the Company’s clinical operations and other programs, and an increase in lab supplies. Research and development expenses for the nine months ended September 30, 2018 were $38.2 million, compared to $35.1 million for the same period in 2017.

G&A Expenses: General and administrative expenses for the third quarter ended September 30, 2018 were $3.6 million, compared to $1.9 million for the same period in 2017. The increase was primarily due to higher legal and accounting fees and additional staff in key areas required to support a public company infrastructure, as well as increased facilities and office expenses related to our expanded facility in Hayward. General and administrative expenses for the nine months ended September 30, 2018 were $10.0 million, compared to $5.2 million for the same period of 2017.

Net Loss: Net loss for the third quarter ended September 30, 2018 was $10.8 million, compared to $23.1 million for the same period in 2017. The decrease in net loss was primarily attributable to the increase in revenue and changes in operating expenses noted above. Net loss for the nine months ended September 30, 2018 was $37.3 million, compared to $39.9 million for the same period in 2017.

Based on its current operating plan, the Company expects that its cash and investments as of September 30, 2018 will enable the Company to fund its anticipated operating expenses and capital expenditure requirements into 2021.