On June 6, 2021 Innovent Biologics, Inc. ("Innovent", HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, reported that the results of the Phase Ia/Ib study of IBI110 were released today in a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2021 (Abstract #2589) (Press release, Innovent Biologics, JUN 6, 2021, View Source [SID1234583622]).

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The phase 1 study of IBI110 is a dose-escalation trial evaluating IBI110, an anti-LAG-3 monoclonal antibody, as a single agent and in combination with sintilimab in patients with advanced solid tumors refractory to standard of care therapy. The study is comprised of Phase Ia, an IBI110 single-drug dose-escalation phase, and Phase Ib, the dose-escalation phase of IBI110 in combination with sintilimab (200mg). At disease progression, cross over from IBI110 monotherapy to combo (IBI110+ sintlilimab) was allowed at the investigators’ discretion. At data cutoff (February 9, 2021), 40 patients were enrolled and received treatment. 22 subjects were assigned in dose groups of 7 (0.01mg/kg~20mg/kg) in Phase Ia, the prespecified dose escalation had been completed and no dose-limited toxicity (DLT) was observed. No adverse event (AE) led to discontinuation of IBI110 or sintilimab and no treatment-related death was reported. In terms of efficacy, a subject with advanced ovarian cancer who progressed on multiple prior systemic therapies achieved partial response after IBI110 monotherapy treatment and was still in the study for more than 6 months. 18 subjects were assigned in dose groups of 5 (0.3mg/kg~5mg/kg) in Phase Ib of IBI110 in combination with sintilimab, the prespecified dose escalation had been completed and no dose-limited toxicity (DLT), adverse events leading to discontinuation or death was observed. At data cutoff (April 26, 2021), three subjects had achieved partial response with an objective response rate of 16.7% (3/18) in phase 1b, demonstrating a synergistic anti-tumor activity of IBI110 and sintilimab.

"The efficacy signal and safety profile we see with IBI110 in this study is exciting," said Dr. Hui Zhou, Senior Vice President of Clinical Development, Innovent Biologics. "The single-drug efficacy demonstrated in the trial suggested a huge anti-tumor potential of this target. As we move ahead with the study, we look forward to greater clinical benefits of IBI110 in combination with sintilimab in patients in this trial. We are committed to innovation and relentless pursuit of breakthroughs for cancer patients. Aside from IBI110, we are also initiating phase 1 clinical trial on IBI323, a LAG-3/PD-L1 bispecific antibody, to fully investigate therapeutic value of LAG-3. "

Professor Caicun Zhou from Shanghai Pulmonary Hospital said: "IBI110’s good safety and preliminary efficacy data support the further exploration of this molecule in a variety of tumor types, including non-small cell lung cancer, small cell lung cancer, melanoma, etc. LAG-3 is the third validated immune-related target after PD-1 and CTLA-4. We look forward to seeing more positive results from the upcoming trials of IBI110."

About the Study

This study is a phase Ia/Ib open label, dose escalation and expansion study to evaluate the safety, tolerability and efficacy of IBI110, an anti-LAG-3 monoclonal antibody, as a single agent and in combination with sintilimab in advanced solid tumors. The study follows a classic 3+3 design. Patients received escalating doses of IBI110 once every 3 weeks in phase Ia and escalating doses of IBI110 in combination with TYVYT (sintilimab injection) 200 mg once every 3 weeks in phase Ib until disease progression, unacceptable toxicity, or withdrawal of consent.

Primary objectives of the trial were to evaluate the safety, tolerability and the antitumor activity of IBI110 monotherapy and in combination with sintilimab.

About LAG-3

Lymphocyte activation gene-3 (LAG-3) (CD223) is a novel 498-amino acid type I transmembrane protein identified on activated human NK and T-cell lines. LAG-3 (CD223) is a potential cancer immunotherapeutic target due to its negative regulatory role on T cells and its capacity, in combination with PD-1, to mediate a state of exhaustion.

About TYVYT (sintilimab Injection)

TYVYT (sintilimab injection) is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Lilly. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, TYVYT (sintilimab Injection) has been approved for two indications, including:

The treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy
In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of nonsquamous non-small cell lung cancer
In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer
Additionally, Innovent currently has regulatory submissions under review in China for TYVYT (sintilimab Injection):

In combination with BYVASDA (bevacizumab injection) for the first-line treatment of hepatocellular carcinoma
The second-line treatment of squamous non-small cell lung cancer
In May 2021, the U.S. FDA accepted for review the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of nonsquamous non-small cell lung cancer.

TYVYT (sintilimab Injection) was included in China’s National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 included in the list in that year.

On June 6, 2021 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies, reported updated clinical data for lifileucel from Cohort 2 in the C-144-01 clinical study in patients with advanced melanoma (Press release, Iovance Biotherapeutics, JUN 6, 2021, View Source [SID1234583614]). The data were presented in an oral presentation at the ASCO (Free ASCO Whitepaper) 2021 Annual Meeting.

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Omid Hamid, M.D., Chief of Research/Immuno-Oncology, The Angeles Clinic & Research Institute, stated, "Anti-PD-1 therapy is a mainstay class of treatment offering several therapeutic options for metastatic melanoma. For patients who progress on anti-PD-1 therapy, there is an unfulfilled need for efficacious and durable treatment options. The latest results with lifileucel suggest that early intervention with lifileucel TIL therapy, immediately upon progression on anti-PD-1 therapy, may offer better outcomes and longer duration of response. These data offer evidence that patients have had positive treatment experiences with lifileucel, and I believe TIL therapy has the potential to become an important option within the melanoma treatment landscape."

Friedrich Graf Finckenstein, M.D., Chief Medical Officer of Iovance, stated, "Our latest data for Cohort 2 in the C-144-01 clinical study are very exciting and continue to support the durability of responses after lifileucel in challenging to treat patients with melanoma. Median DOR has still not been reached at 33 months of median study follow up. We are also reporting the important observation that a shorter duration of prior anti-PD-1 therapy is associated with longer duration of response after lifileucel. We are committed to bringing lifileucel to patients as soon as we can."

The long-term follow-up data for Cohort 2 in the C-144-01 clinical study continue to demonstrate durability and depth of lifileucel TIL therapy response. Median DOR was not reached at 33.1 months of median study follow up (range: 2.2 to 38.5+ months) and Overall Response Rate, or ORR, remained at 36.4% (data extraction: April 2021). Responses deepened over time and one patient converted from partial to complete response at 24 months post lifileucel infusion.

A multivariable model showed that for every six-month decrease in cumulative duration of prior anti-PD-1 therapy, DOR to lifileucel will be nearly doubled. These results suggest that early intervention with lifileucel at the time of initial progression on anti-PD-1 therapy may maximize benefit.

All patients in Cohort 2 had high baseline disease burden and were heavily pretreated (3.3 mean prior therapies), including anti-PD1 and BRAF/MEK inhibitors if BRAFV600 mutation positive. The adverse event profile was consistent with the underlying advanced disease, lymphodepletion and IL-2 regimens, with no new safety risks identified for lifileucel during long-term follow-up.

Iovance Presentation at ASCO (Free ASCO Whitepaper) 2021
Title: Lifileucel (LN-144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in patients with advanced melanoma: Evaluation of impact of prior anti-PD-1 therapy.
Authors: James M. G. Larkin, et al.
Session Title: Melanoma/Skin Cancers
Session Type: Oral Abstract Session
Abstract Number: 9505
Location: ASCO (Free ASCO Whitepaper) Meeting Library at View Source and View Source
Session Date and Time: Sunday, June 6, 2021 from 8:00 – 11:00 a.m. ET
Webcast and Conference Call
Iovance will host a webcast and conference call on Sunday, June 6, at 12:00 p.m. ET to discuss ASCO (Free ASCO Whitepaper) clinical data updates for lifileucel alone and in combination with pembrolizumab in patients with advanced melanoma. Iovance senior leadership, together with Dr. Hamid, will present a summary of the ASCO (Free ASCO Whitepaper) data from Cohort 1A in the IOV-COM-202 study as well as the oral presentation of updated Cohort 2 data from the C-144-01 clinical study.

The conference call dial-in numbers are 1-844-646-4465 (domestic) or 1-615-247-0257 (international) and the access code is 4858337. The live webcast can be accessed in the Investors section of the company’s website at View Source The archived webcast will be available for a year in the Investors section at www.iovance.com.

On June 6, 2021 OriginCell Therapeutics (Shanghai) Co., Ltd. ("OriginCell"), together with Lishui Central Hospital affiliated to Zhejiang University and Shanghai Changzheng Hospital, reported the updated data from the on-going trial of Ori-CAR-001, a GPC3 CAR-T cell therapy for the treatment of relapsed/refractory hepatocellular carcinoma (HCC), at the 2021 annual meeting of American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (Press release, Shanghai OriginCell Therapeutics, JUN 6, 2021, View Source [SID1234583618]). Preliminary results from the study show promising safety and efficacy of Ori-CAR-001 in patients with GPC3-positive relapsed/refractory HCC.

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(PRNewsfoto/Yuanqi Biological Technology (Shanghai) Co., Ltd.)(PRNewsfoto/Yuanqi Biological Technology (Shanghai) Co., Ltd.)
Session type: Poster Session
Abstract Title: An armored GPC3-directed CAR-T for refractory or relapsed hepatocellular carcinoma in China: A phase I trial
Date and time: 06/04/2021, 9:00 AM (EDT)
Abstract ID: 4095
Link: View Source

A breakthrough Cell Therapy against Solid Tumors

As of March 10, 2021, a total of 11 patients were enrolled into this study. All subjects had advanced HCC and had failed prior lines of treatment including chemotherapy, TACE, and targeted therapies. All subjects had BCLC stage C (late stage) HCC except for one subject with stage B (mid stage). All subjects had multiple lesions, of which 6 (54%) had distant metastasis. Two subjects dropped out early and were not evaluable. Among the 9 evaluable subjects, 4 achieved partial response (PR), 3 achieved stable disease (SD), and 2 had disease progression (PD). The objective response rate was 44.4%, and the disease control rate reached 77.8%. A partial response lasting for more than 6 months was observed in Subject 007 at the time of data cutoff, whose tumor volume was reduced by more than 80% one month post cell therapy infusion. (As of June 2021, this subject had exceeded 8 months of disease control, follow-up is still ongoing). Good tumor response was also seen in Subject 012, who has advanced and diffuse massive HCC and joined the study after failing in radiotherapy, targeted drug and 12 times of TACE.

Barcelona Clinic Liver Cancer (BCLC) is a liver cancer staging system developed by the European Association for the Study of Liver, to help assess patients’ conditions, select the right therapies for the right patients, and predict patients’ prognosis. The BCLC system classifies HCC mainly as stages of 0, A, A1,A2,A3,A4, B, C,and D.

On day 28 post infusion with CAR-T cells, the target tumor lesion decreased from 133mm in diameter at baseline to 9mm, a reduction of more than 93%. Currently, the subject is being evaluated for month 3 post CAR-T cell infusion, MRI scan showed near complete tumor response. In addition, AFP level (alpha-fetoprotein, a specific tumor marker for primary liver cancer) decreased from a baseline value of >80,000/ng/ml to 1148.9 ng/ml on month 1, and to 746.7 ng/ml at month 3 post infusion (normal range <40ng/ml), demonstrating significant preliminary efficacy of Ori-CAR-001 in patients with advanced HCC.

Good Safety Profile

Ori-CAR-001 CAR-T infusion demonstrated good safety and tolerability in 11 patients. Cytokine release syndrome (CRS) was observed in 9 patients (7 cases grade 1-2 and 2 cases grade 4), which were resolved after treatment with steroids and tocilizumab. No neurotoxicity was observed.

Regarding the results from this exploratory study, Professor Ji Jiansong, principal investigator of Lishui Central hospital, who is also Chief scientist of the National Key R&D Program, director of Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research of Zhejiang China, said, "There is currently no effective treatment for relapsed/refractory hepatocellular carcinoma. Many challenges such as the tumor micro environment is difficult to overcome and have limited the therapeutic effects of cell therapy in solid tumors. However, Ori-CAR-001, developed by OriginCell Therapeutics, has managed to achieve an objective response rate of 44% and a disease control rate of 77% in patients with relapsed/refractory HCC, demonstrating a level of safety and anti-tumor activity that cannot be achieved by currently available drugs. Given its preliminary promising efficacy and safety data, we are confident in the future development prospects of Ori-CAR-001 and will continue our research studies. We take great pride and hope Ori-CAR-001 will one day become a new treatment option for patients with advanced HCC.

Dr. He Xiaowen, co-founder and chief scientific officer of OriginCell Therapeutics, said, " Although Immuno-cell therapies have produced remarkable clinical responses in hematological tumors, they have limited efficacy against solid tumors. OrginCell will continue to explore the broader unmet needs in this space, with the hope to bring more effective immuno-cell therapies to clinicians and patients with advanced stage cancer."

About Ori-CAR-001

Ori-CAR-001 is a next generation autologous chimeric antigen receptor T cell therapy targeting GPC3 for the treatment of refractory/ relapsed hepatocellular carcinoma (HCC). The construct of Ori-CAR-001 is comprised of humanized anti-GPC3 scFv, a CD8-derived hinge region, a transmembrane domain linked to 4-1BB co-stimulatory domain, a CD3z intracellular signaling domain, and Ori2 components simultaneously expressed through T2A. Compared with conventional CAR-T cells, Ori-CAR-001 has significantly higher proportion of memory stem T cells, which may translate to improved expansion and persistence in the body, thereby increasing their anti-tumor activity.

It is worth noting that, in addition to the preliminary safety and efficacy data of Ori-CAR-001 presented at 2021 ASCO (Free ASCO Whitepaper) annual meeting, OriginCell and study investigators also carried out translational medicine studies, in which the mode of administration, dosing, PK/PD, and biomarkers were explored. This will futher promote the application and development of cell therapy for solid tumors.

OriginCell will plan more clinical development programs to further explore Ori-CAR-001’s potential based on existing data, and the Investigational New Drug (IND) application with the National Medical Products Administration (NPMA) is currently in progress.

About ASCO (Free ASCO Whitepaper)

With more than 40,000 members from more than 100 countries, the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) is the world’s leading academic organization for physicians and oncology professionals caring for people with cancer. Its mission is to prevent cancer and improve cancer care, and promote the translation of research findings into clinical practice. By providing access to a global network of oncology expertise, the ASCO (Free ASCO Whitepaper) annual meeting is recognized as the world’s most influential academic congress in the field of oncology.

On June 6, 2021 Autobahn Labs, an early-stage drug discovery incubator, reported a new strategic venture collaboration with Cold Spring Harbor Laboratory (CSHL) (Press release, Evotec, JUN 6, 2021, View Source;announcements/press-releases/p/autobahn-labs-incubator-announces-partnership-with-cold-spring-harbor-laboratory-to-advance-novel-science-to-the-clinic-6068 [SID1234583737]). Together with Autobahn Labs, CSHL will identify promising research programs with therapeutic potential and partner to form promising new drug discovery companies.

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"We’re delighted to partner with CSHL, expanding our reach and collaborations with top faculty working on truly compelling science with strong therapeutic potential," said Thomas Novak, PhD, Chief Scientific Officer of Autobahn Labs. "Cold Spring Harbor is a close-knit and collegial campus that also has cultivated one of the premier scientific meeting programs in the world."

"Autobahn has the ability to get involved early and put their resources into CSHL’s drug discovery programs and generate a pipeline of highly investable spin-out companies," said Andrew Whiteley, CSHL Vice President, Business Development and Technology Transfer. "This collaboration will enable us to more quickly advance our basic biology expertise from the lab to the clinic."

Under terms of the agreements with CSHL, Autobahn Labs will invest up to $5M in funding and biopharmaceutical services into specific programs yet to be identified. Since its launch in June 2020, Autobahn Labs has announced partnerships with four leading institutions and has started two new drug discovery programs.

Backed by Samsara BioCapital, Evotec SE, and KCK Ltd, Autobahn Labs invests earlier than traditional venture financing models, providing intellectual, financial and physical capital to efficiently and effectively advance new scientific discoveries from novel concept to preclinical drug candidate. Institutions benefit from Autobahn’s strategy and operational support, as well as the industry-leading drug discovery capabilities of Evotec, a global leader in drug discovery and development. Pre-agreement on many of the economic and intellectual property terms that govern the relationship further facilitates the negotiation and creation of jointly-owned new companies.

On June 5, 2021 Samsung Pharm Co., Ltd. reported that the company presented the results of a phase III clinical trial of its pancreatic cancer immunotherapeutic drug candidate called ‘RIAVAX (GV1001)’ conducted in Korea at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual meeting (Press release, GemVax, JUN 5, 2021, View Source;gemvax-present-pancreatic-cancer-immunotherapeutic-drug-riavax-phase-iii-results-at-asco-2021-301306066.html [SID1234583623]).

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ASCO 2021, which celebrates its 57th anniversary this year, runs from June 4th to June 8th and will be held virtually due to COVID-19. Some 4500 experts in the field gather every year to share and discuss the results of leading clinical research and advance cancer research and development.

‘RIAVAX ( GV1001)’ is a peptide drug derived from human telomerase consisting of 16 amino acids. It has been developed as an immunotherapeutic drug for pancreatic cancer which works to activate immune cells to attack the cancer cells. It is known to extend survival in pancreatic cancer patients with high serum eotaxin levels when administered in combination with the current chemotherapy, Gemcitabine/Capecitabine.

The RIAVAX Phase III clinical trial was conducted to investigate safety and efficacy when given in combination with Gemcitabine/Capecitabine in 148 patients with locally advanced and metastatic pancreatic cancer at 16 hospitals across Korea, including the Severance Hospital.

The results of the clinical trial showed median overall survival (OS) of 11.3 months in the treatment group compared to 7.5 months in the control group, with statistically significant improvement (p=0.021). Another key endpoint which is time to tumor progression (TTP) also showed a statistical significance with 7.3 months in the treatment group compared with 4.5 months in the control group (p=0.021). No specific safety issues were reported. These results indicate that RIAVAX should be considered as one of the treatment options for patients with locally advanced and metastatic pancreatic cancer with high serum eotaxin levels.

Samsung Pharm in-licensed domestic rights to RIAVAX from its affiliate, GemVax & KAEL Co., Ltd. in 2014. GemVax & KAEL conducted a large-scale Phase III clinical trial of RIAVAX (‘TeloVac’) in the United Kingdom from 2007 to 2011, with 1,062 locally advanced and metastatic pancreatic cancer patients. The results of the TeloVac study were presented at 2013 ASCO (Free ASCO Whitepaper) followed by the presentation an analysis of the correlation between the high eotaxin level and improved survivals in pancreatic cancer patients administered with GV1001 at 2014 ASCO (Free ASCO Whitepaper).