1stOncology™: Cancer Intelligence Service – Page 9249 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Therapeutic Solutions International Reports Amplification of Cancer Specific Immune Responses Using Second Generation Tumor Endothelial Targeting Vaccine StemVacs-V iPSC

On June 7, 2021 Therapeutic Solutions International, Inc., (OTC Markets: TSOI), reported potent synergy between its tumor blood vessel targeting StemVacs-V iPSC immunotherapy and several classical tumor specific therapeutic vaccines (Press release, Therapeutics Solutions International, JUN 7, 2021, View Source [SID1234583681]).

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!

In a series of experiments tumor growth administration of dead tumor cells together with StemVacs-V resulted in potent immunological memory to the tumor cells, which could be transferred to immunologically naïve mice. Additionally, the experiments demonstrated killing tumor cells using conventional approaches such as chemotherapy, when performed together with StemVacs-V iPSC, led to the development of immunological memory towards the specific cancer.

"By targeting the blood vessels that feed the cancer, StemVacs-V iPSC causes enhanced necrotic cell death, which stimulates systemic immunity against the cancer throughout the whole body," said Dr. James Veltmeyer, Chief Medical Officer of the Company. "We are extremely enthusiastic by the current data showing that our blood vessel targeting approach can be used to synergize with both cancer immunotherapies and non-immune therapies of cancer such as chemotherapy and radiation therapy."

Despite cancer immunotherapy being an over 100 billion dollar a year market in 2020, most cancers still do not respond to this approach. These are called "cold tumors." It is believed that by starving the cancer of its blood supply, StemVacs-V iPSC may convert cold tumors to immunotherapy sensitive "hot tumors."

"The potential implications of the current data, which is covered by our previously filed patents, include synergies with oncolytic viruses, checkpoint inhibitors, fractionated radiation therapy, antibodies, and chemotherapies," said Famela Ramos, Vice President of Business Development for Therapeutic Solutions International. "We are currently exploring numerous co-development partnerships."

"This new finding is extremely exciting because it opens the door to synergies with other immunotherapies such as CAR-T therapies, which although successful in liquid tumors, to date have not yielded promising results in solid and/or cold tumors," said Timothy Dixon, President and CEO of the Company. "Having SAB members such as Santosh Kesari and Francesco Marincola, who are at the forefront of cancer immunotherapy, significantly positions us to accelerate the development of our new approach which targets the "Achille’s Heel of cancer."

Bausch Health Announces Early Tender Results And Early Settlement Date For Cash Tender Offer For Senior Secured Notes

On June 7, 2021 Bausch Health Companies Inc. (NYSE/TSX: BHC) ("Bausch Health," the "Company" or the "Offeror") reported the results to date of its pending cash tender offer (the "Tender Oﬀer"), to purchase any and all of its outstanding 7.00% Senior Secured Notes due 2024 (the "Notes"), as well as the anticipated early settlement date for the Tender Offer on June 8, 2021 (the "Early Settlement Date") (Press release, Bausch Health, JUN 7, 2021, View Source [SID1234583680]).

The terms and conditions of the Tender Offer are described in an Oﬀer to Purchase dated May 24, 2021 (as it may be amended or supplemented from time to time, the "Offer to Purchase"). All terms and conditions of the Tender Offer remain unchanged as set forth in the Offer to Purchase.

As of 5:00 p.m., New York City time, on June 7, 2021 (the "Early Tender Date"), the aggregate principal amount of Notes validly tendered and not validly withdrawn is $545,079,000. The Offeror expects to accept for purchase all of the Notes validly tendered prior to the Early Tender Date, subject to the satisfaction of the conditions to such Tender Offer. The Offeror expects that the conditions to the Tender Offer will be satisfied as of the Early Settlement Date.

The total consideration for each $1,000 principal amount of Notes is $1,019.25 plus accrued and unpaid interest (the "Total Consideration") and is expected to be paid on the Early Settlement Date to the holders of Notes tendered and accepted for purchase as of the Early Tender Date. The Total Consideration includes an early tender premium of $30.00 per $1,000 principal amount of Notes accepted for purchase as of the Early Tender Date. In addition to the Total Consideration, all Holders of Notes accepted for purchase pursuant to the Tender Offer will also receive accrued and unpaid interest on the Notes from the last interest payment date to, but not including, the Early Settlement Date.

The Tender Offer remains open and will expire at 11:59 p.m., New York City time, on June 21, 2021 (such date and time, as it may be extended, the "Expiration Date"). No tenders will be valid if submitted after the Expiration Date. The Offeror expects to purchase any remaining Notes tendered following the Early Settlement Date that have been validly tendered at or prior to the Expiration Date and accepted for purchase, subject to all conditions to the Tender Offer having been either satisfied or waived by the Offeror, promptly following the Expiration Date (the date of such acceptance and purchase, the "Final Settlement Date"). The Final Settlement Date is expected to occur on the second business day following the Expiration Date, assuming the conditions to the Tender Offer and the Solicitation have been either satisfied or waived by the Offeror at or prior to the Expiration Date and all of the outstanding Notes are not purchased on the Early Settlement Date.

The Tender Oﬀer is subject to, and conditioned upon, the satisfaction or waiver of certain conditions described in the Offer to Purchase, including the completion of the Company’s previously announced private offering of $1.6 billion aggregate principal amount senior secured notes, on terms acceptable to the Company.

The deadline for holders to validly withdraw tenders of Notes has passed. Accordingly, Notes that were already tendered at the Early Tender Date and any additional Notes that are tendered at or prior to the Expiration Date may not be withdrawn, except in certain limited circumstances where additional withdrawal rights are required by law.

If, following the consummation of the Tender Offer, any Notes remain outstanding, the Offeror intends to redeem such Notes in accordance with terms of the Notes and the indenture, dated as of March 21, 2017 (as amended or supplemented), among Bausch Health, the subsidiaries signatory thereto, The Bank of New York Mellon, as trustee, and the notes collateral agents party thereto under which the Notes were issued.

Goldman Sachs & Co. LLC is acting as the dealer manager in the Tender Offer. Global Bondholder Services Corporation has been retained to serve as both the depositary and the information agent for the Tender Offer. Persons with questions regarding the Tender Offer should contact Goldman Sachs & Co. LLC at (collect) (212) 902-5962 or (toll free) (800) 828-3182. Requests for copies of the Offer to Purchase and other related materials should be directed to Global Bondholder Services Corporation at (toll-free) (866) 470-3800 or (collect) (212) 430-3774.

None of the Offeror, its board of directors or officers, the dealer manager, the depositary, the information agent or the trustee with respect to the Notes, or any of their respective affiliates, makes any recommendation that holders tender or refrain from tendering all or any portion of the principal amount of their Notes, and no one has been authorized by any of them to make such a recommendation. Holders must make their own decision as to whether to tender their Notes and, if so, the principal amount of Notes to tender. The Tender Offer is made only by the Offer to Purchase. This news release is neither an offer to purchase nor a solicitation of an offer to sell any notes in the Tender Offer. The Tender Offer is not being made to holders of Notes in any jurisdiction in which the making or acceptance thereof would not be in compliance with the securities, blue sky or other laws of such jurisdiction. In any jurisdiction in which the Tender Offer is required to be made by a licensed broker or dealer, the Tender Offer will be deemed to be made on behalf of the Offeror by the dealer manager or one or more registered brokers or dealers that are licensed under the laws of such jurisdiction.

Any securities issued pursuant to the financing transactions described above will not be registered under the Securities Act of 1933, as amended (the "Securities Act"), or any state securities law and may not be offered or sold in the United States absent registration or an applicable exemption from registration under the Securities Act and applicable state securities laws. Such securities have not been and will not be qualified for sale to the public by prospectus under applicable Canadian securities laws and, accordingly, any offer and sale of the securities in Canada will be made on a basis which is exempt from the prospectus requirements of such securities laws.

Live from ASCO 2021 | Ascentage Pharma Presents Updated Results of MDM2-p53 Inhibitor Alrizomadlin (APG-115) Demonstrating an ORR of 24.1% Including Complete Response in Combination with Pembrolizumab in Patients with Advanced Melanoma Resistant or Refractory to Prior Immuno-Oncologic Drugs

On June 7, 2021 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported in an oral presentation at the 57th American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, updated results from a Phase II study of the MDM2-p53 inhibitor alrizomadlin (APG-115) in combination with pembrolizumab in patients with unresectable or metastatic melanoma or advanced solid tumors that have progressed on prior immuno-oncologic (IO) drugs (Press release, Ascentage Pharma, JUN 7, 2021, View Source;ascentage-pharma-presents-updated-results-of-mdm2-p53-inhibitor-alrizomadlin-apg-115-demonstrating-an-orr-of-24-1-including-complete-response-in-combination-with-pembrolizumab-in-patients-with-advanced-mel-301307261.html [SID1234583679]).

As a leading Chinese biotechnology company with progressive visibility at international scientific congresses in recent years, Ascentage Pharma’s clinical study results have been selected for presentations at the ASCO (Free ASCO Whitepaper) Annual Meeting for the fourth year. This year, results from four of its studies clinical studies were selected for presentations at the meeting, including two oral presentations. The clinical study data from the on-going Phase II study of alrizomadlin have demonstrated a manageable safety profile and meaningful clinical antitumor activity, including one patient with a complete response (CR), an objective response rate (ORR) of 24.1% and a disease control rate (DCR) of 55.2% in the PD-1/PD-L1 inhibitor-resistant melanoma cohort. In addition, partial responses (PRs) were reported in enrolled patients with other tumor types.

"The clinical data of alrizomadlin presented in our oral presentation are encouraging, as they suggest clinical activity in hard-to-treat tumor types across multiple indications, including several without currently available standard of care, such as relapsed or refractory melanoma subtypes," said Dr. Anthony W. Tolcher, Founder and CEO of NEXT Oncology, Director of Clinical Research at Texas Oncology, and the Global Principal Investigator of the study. "Our data provide a clinical validation of the recently published paper in Nature Immunology demonstrating that alrizomadlin synergizes with immunotherapy by sustaining STAT5 stability and controlling T-cell-mediated antitumor immunity via the novel pathway of MDM2 inhibition. This seminal publication elucidates why patients who previously failed to respond to IO therapy may derive clinical benefit from the addition of alrizomadlin to the IO agent pembrolizumab."

"This study of alrizomadlin in combination with pembrolizumab offers a clinical validation of the therapeutic synergy between MDM2-p53 inhibitors and existing immuno-oncologic drugs and shows the potential as a new treatment option that could bring renewed hope for patients with solid tumors," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "At this year’s ASCO (Free ASCO Whitepaper) Annual Meeting, we have announced results from multiple studies, including that of Alrizomadlin, in two oral presentations and two poster presentations. I am very proud of these advances, which attest to Ascentage Pharma’s robust capabilities in global innovation. Moving forward, we will remain committed to our mission of addressing unmet clinical needs in China and around the world, and strive to accelerate our clinical programs in the hope of soon benefitting patients."

An overview of the four abstracts presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting:

Drug Candidate

Abstract Title

Abstract #

Format

Lisaftoclax

(APG-2575)

First-in-human study of lisaftoclax (APG-2575), a novel Bcl-2 inhibitor (Bcl-2i), in patients (pts) with relapsed/refractory (R/R) CLL and other hematologic malignancies (HMs)

7502

Oral

Presentation

Alrizomadlin

(APG-115)

Preliminary results of a phase II study of alrizomadlin (APG-115), a novel, small-molecule MDM2 inhibitor, in combination with pembrolizumab in patients (pts) with unresectable or metastatic melanoma or advanced solid tumors that have failed immuno-oncologic (I-O) drugs

2506

Oral

Presentation

Trial in progress: A phase I/II trial of novel MDM2 inhibitor alrizomadlin (APG-115), with or without platinum chemotherapy, in patients with p53 wild-type salivary gland carcinoma

TPS6094

Poster

Presentation

Pelcitoclax

(APG-1252)

Trial in progress: A multicenter phase Ib/II study of pelcitoclax (APG-1252) in combination with paclitaxel in patients with relapsed/refractory small-cell lung cancer (R/R SCLC)

TPS8589

Poster

Presentation

Highlights of the oral presentation on alrizomadlin at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting:

Abstract: #2506

This open-label, multicenter Phase II study in the US assessed the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of alrizomadlin in combination with pembrolizumab in patients with advanced solid tumors.
As of April 15, 2021, 102 patients had been enrolled in the Phase II part of the study and treated with alrizomadlin at the recommended Phase II dose (RP2D) of 150 mg every other day, in combination with pembrolizumab. This study has 6 cohorts, including patients with: PD-1/PD-L1 inhibitor-resistant melanoma, non-small cell lung cancer (NSCLC), and urothelial carcinoma; or malignant peripheral nerve sheath tumor (MPNST), liposarcoma, and ATM mutant solid tumors.
Antitumor Effects:
In the PD-1/PD-L1 inhibitor-resistant melanoma cohort (n=29), there was 1 confirmed partial response (PR) out of 7 patients with uveal (ocular) melanoma; 2 PRs (1 confirmed + 1 unconfirmed) out of 5 patients with mucosal melanoma; and 1 complete response (CR, confirmed) and 3 PRs (2 confirmed + 1 unconfirmed) out of 15 patients with cutaneous melanoma. The ORR and DCR in the melanoma cohort were 24.1% (7/29) and 55.2% (16/29), respectively.
In the MPNST cohort (n=6), 1 PR (unconfirmed).
In the liposarcoma cohort (n=16), 1 PR (unconfirmed) and 12 stable diseases (SDs), at a DCR of 81.2% (13/16).
In the PD-1/PD-L1 inhibitor-resistant NSCLC (n=15) and urothelial carcinoma (n=8 evaluable) cohorts, 1 patient in each cohort achieved confirmed PR.
Common treatment-related adverse events (TRAEs) observed in more than 10% of patients were nausea, thrombocytopenia, vomiting, fatigue, decreased appetite, diarrhea, neutropenia, and anemia.
In conclusion, alrizomadlin combined with pembrolizumab is well tolerated, and did not exhibit any overlapping toxicity. These preliminary results have established proof of concept clinically that the combination regimen has antitumor activity in patients with IO relapsed/refractory metastatic melanoma, (including uveal melanoma, mucosal melanoma, or cutaneous melanoma). In addition, this combination therapy also showed promising antitumor activity in patients with MPNST or liposarcoma for which pembrolizumab has no approved indications.

Live from ASCO 2021 | Ascentage Pharma Delivers Oral Presentation Featuring Updated Data Demonstrating Promising Efficacy and Safety of Bcl-2 Inhibitor Lisaftoclax (APG-2575) in Patients with Relapsed or Refractory CLL/SLL

On June 7, 2021 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported updated results from the first-in-human study of the Bcl-2 inhibitor lisaftoclax (APG-2575) in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (R/R CLL/SLL) and other hematologic malignancies (Press release, Ascentage Pharma, JUN 7, 2021, View Source;ascentage-pharma-delivers-oral-presentation-featuring-updated-data-demonstrating-promising-efficacy-and-safety-of-bcl-2-inhibitor-lisaftoclax-apg-2575-in-patients-with-relapsed-or-refractory-cllsll-301307266.html [SID1234583678]). The findings were reported in an oral presentation at the 57th American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

As one of the Chinese biotechnology companies that have been increasingly visible at international scientific congresses in recent years, Ascentage Pharma has entered the fourth year in which its clinical advances have been selected for presentations at the ASCO (Free ASCO Whitepaper) Annual Meeting. This year, results from four of the company’s clinical trials were selected for presentations at the meeting, and of these data, the two oral presentations have received widespread and avid interest from research and medical communities. Updated data on lisaftoclax have demonstrated favorable preliminary safety and efficacy, including an objective response rate (ORR) of 80% and a favorable tolerability profile, with manageable adverse events (AEs) in patients with R/R CLL/SLL. Moreover, no dose-limiting toxicity (DLT) was observed at the maximum tested dose of 1,200 mg. The maximum tolerated dose (MTD) has not been reached, and no laboratory or clinical tumor lysis syndrome (TLS) has been reported.

Dr. Asher Chanan-Khan, MD, of Mayo Clinic, and the Global Principal Investigator of this study, commented: "Lisaftoclax is a potent, selective Bcl-2 inhibitor which can both induce apoptosis and inhibit tumor cell growth. In this first-in-human study in the US and Australia, lisaftoclax showed a favorable safety profile and promising antitumor activity in patients with R/R CLL/SLL, and potential disease control in several other hematologic malignancies. In view of the preliminary safety and clinical activity observed in this Phase I study, we look forward to further evaluating the antitumor activity of lisaftoclax in individual hematologic malignancies and solid tumors."

"The initial objective response rate of 80%, together with a favorable safety profile and no TLS despite a daily dose ramp-up, demonstrated by lisaftoclax in patients with R/R CLL/SLL are particularly encouraging and once again support the best-in-class potential of lisaftoclax," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "At this year’s ASCO (Free ASCO Whitepaper) Annual Meeting, we have announced results from multiple studies, including that of lisaftoclax, in two oral presentations and two poster presentations. I am very proud of these advances, which attest to Ascentage Pharma’s robust capabilities in global innovation. Moving forward, we will remain committed to our mission of addressing unmet clinical needs in China and around the world, and strive to accelerate our clinical programs in the hope of soon benefitting patients."

An overview of the four abstracts presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting:

Drug Candidate

Abstract Title

Abstract #

Format

Lisaftoclax

(APG-2575)

First-in-human study of lisaftoclax (APG-2575), a novel Bcl-2 inhibitor (Bcl-2i), in patients (pts) with relapsed/refractory (R/R) CLL and other hematologic malignancies (HMs)

7502

Oral

Presentation

Alrizomadlin

(APG-115)

2506

Oral

Presentation

Trial in progress: A phase I/II trial of novel MDM2 inhibitor alrizomadlin (APG-115), with or without platinum chemotherapy, in patients with p53 wild-type salivary gland carcinoma

TPS6094

Poster

Presentation

Pelcitoclax

(APG-1252)

Trial in progress: A multicenter phase Ib/II study of pelcitoclax (APG-1252) in combination with paclitaxel in patients with relapsed/refractory small-cell lung cancer (R/R SCLC)

TPS8589

Poster

Presentation

Highlights of the oral presentation on lisaftoclax at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting:

First-in-human study of lisaftoclax (APG-2575), a novel Bcl-2 inhibitor (Bcl-2i), in patients (pts) with relapsed/refractory (R/R) CLL and other hematologic malignancies (HMs)

Abstract: #7502

This first-in-human global Phase I study assessed the safety, pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and MTD/recommended Phase II dose (RP2D) of lisaftoclax in patients with R/R CLL and other HMs. Lisaftoclax was orally administered once daily in a 28-day cycle. Patients with CLL or intermediate-high TLS risk were initiated on a daily ramp-up schedule until the dose assigned before the study cycles.
As of April 15, 2021, 36 patients had been enrolled and treated with lisaftoclax at doses ranging from 20 to 1,200 mg, with a median of 2 (range: 1-13) prior lines of treatment. These patients had been diagnosed with R/R CLL/SLL (n=15), multiple myeloma (MM, n=6), follicular lymphoma (FL, n=5), Waldenström macroglobulinemia (WM, n=5); and either acute myeloid leukemia (AML), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), myelodysplastic syndromes (MDS), or hairy cell leukemia (HCL; n=1 each). These patients received a median of 6 cycles (range: 1-24) of treatment with lisaftoclax.
Lisaftoclax was well tolerated, with manageable AEs. No DLT was observed even at the maximum dose of 1,200 mg. The MTD has not been reached, and no laboratory or clinical TLS has been reported. Hematologic treatment-related adverse events (TRAEs) of any grade in more than 10% patients included neutropenia and anemia, while nonhematologic TRAEs included fatigue, diarrhea, constipation, and nausea.
In the 15 evaluable patients with R/R CLL/SLL, 7 (46.7%) each were assessed as Rai stage III-IV or intermediate-high per International Prognostic Index (IPI). Patients in this cohort received a median of 9 (range: 5-24) cycles of treatment, and 12 patients achieved partial responses (PRs), for an ORR of 80% and a median time to response of 2 (range: 2-8) treatment cycles.
Among 21 patients with R/R non CLL/SLL, who received a median of 3 (range: 1-13) prior lines of treatment, 20 were evaluable. Of these individuals, 1 with t (11;14)-mutant MM achieved minor response (MR) after 2 treatment cycles. A total of 10 (50%) patients in this cohort achieved stable disease (SD) or deeper responses.
The preliminary PK profile showed that exposures increased with lisaftoclax at doses ranging from 20 to 1,200 mg (average half-life: 4-5 hours). On BH3 profiling, lisaftoclax rapidly triggered changes in Bcl-2 complex in CLL/SLL patient samples, which were consistent with rapid clinical reductions in absolute lymphocyte counts (ALCs).
In conclusion, efficacy and safety data showed that the Bcl-2 inhibitor lisaftoclax offers a potential alternative treatment for patients with R/R CLL/SLL and other HMs, with a daily ramp-up schedule that may be more patient-friendly and a favorable preliminary safety profile.

Innovent Biologics and IASO Biotherapeutics to Present Updated Data from its Anti-BCMA CAR-T Therapy in Relapsed/Refractory Multiple Myeloma at European Hematology Association (EHA) Congress

On June 7, 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, together with IASO Biotherapeutics (IASO Bio), reported to deliver an oral presentation on updated data from the Phase I study of IBI326 in patients with relapsed/refractory multiple myeloma (R/R MM) at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress, June 9-17, 2021 (Press release, Innovent Biologics, JUN 7, 2021, View Source [SID1234583677]). The presentation will further demonstrate the safety, efficacy, and increased persistence of IBI326.

IBI326 is a fully-human B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy co-developed by IASO Bio and Innovent (Innovent: IBI326, IASO Bio: CT103A), and it is currently under the pivotal Phase II clinical trial. In February 2021, IBI326 was granted the Breakthrough Therapy Designation (BTD) by China regulatory authority, National Medical Production Administration (NMPA) for the treatment of relapsed/refractory multiple myeloma.

In the oral presentation, Professor Chunrui Li with Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology (HUST) in China will report the clinical data on 35 patients with R/R MM, who received 1.0, 3.0, or 6.0 × 106/kg IBI326 treatment respectively in the dose-escalation phase and dose-expansion cohort. The 1.0 × 106/kg dose was determined as Recommended Phase II Dose (RP2D). The median age of the 35 patients was 54 (27, 72). Among them, eight patients had extramedullary multiple myeloma (EMM) and one patient had complication with plasma cell leukemia. The median number of prior treatment regimens was four (3, 12). Ten patients previously received autologous hematopoietic stem cell transplantation (AHSCT), and 10 patients received murine BCMA CAR-T treatment. As of May 1, 2021, the median follow-up of the 35 patients was 291 days (21, 954).

IBI326 has a rapid onset of action and long-lasting efficacy. The overall response rate (ORR) was 97.1% in the 35 patients, among whom 29 patients (82.9%) achieved ≥ VGPR and 20 patients (57.1%) achieved complete response/stringent complete response (CR/sCR). And 34 patients evaluable for MRD achieved minimal residual disease (MRD) negativity, with the median time to MRD negativity 1.3 (0.7, 4.1) months.
All patients previously treated with murine BCMA CAR-T or patients with extramedullary multiple myeloma (EMM) benefited from IBI326. Among all 35 patients, eight were with EMM, among whom eight (75%) achieved ≥VGPR, two (25%) achieved PR, eight patients achieved ≥PR. Among all 35 patients, 10 patients were treated with a prior murine BCMA CAR-T treatment, among whom eight (80%) achieved ≥VGPR, one (10%) achieved PR, one（10%）achieved stable disease (SD).
IBI326 has a good safety profile. Five of the 35 patients had cytokine release syndromes (CRS) of Grade 3 or above. The median time to onset of CRS was 4 (1, 9) days, and all CRS could be efficiently controlled by tocilizumab and/or steroids. ICANS was observed in only one patient whose symptom was drowsiness; the patient later spontaneously relieved without any treatment.
IBI326 was persistent in the patients. The median time to reach the peak of IBI326 expansion in the patients was 12 (7, 17) days. As of the cut-off date, three patients had IBI326 persistence for over two years, and the first patient of them achieved persistent sCR.
IBI326 has lower immunogenicity. Only two patients (5.7%) were detected positive for anti-drug antibody (ADA), and the immunogenicity was significantly lower than that of the prior murine BCMA CAR-T treatment.
The clinical data of the study in patients with R/R MM presented at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in 2019 highlighted the impressive safety profile, efficacy, and durability of response of IBI326. The study also included four patients who had relapsed after prior murine BCMA CAR T-cell treatment. The overall response of these four patients demonstrated that IBI326 can also be an effective treatment option for patients who have relapsed from a prior CAR-T therapy.

In June 2021, the results were published in Blood, a peer-reviewed journal specializing in hematology, in an article titled "A phase 1 Study of a Novel Fully Human BCMA-targeting CAR (IBI326) in Patients with Relapsed/Refractory Multiple Myeloma." The editors of Blood were impressed by the unique persistence of IBI326 and the authors’ exposition on the re-treatment prospects of the disease during the study. Therefore, they invited experts from University College London Cancer Institute to write a review titled "BCMA CARs in multiple myeloma: room for more?" (DOI 10.1182/blood.2021010833).

Dr. Hui Zhou, Senior Vice President of Medical Development, Innovent Biologics, said, "We are glad to see that the excellent clinical data of IBI326 (IASO: CT103aA) has been highly recognized by the EHA (Free EHA Whitepaper) congress. In particular, it still shows good clinical benefits to the patients who received prior murine BACM CAR-T treatment, and provides better treatment options for patients with relapsed/refractory multiple myeloma. We look forward to the launch of this cell therapy to benefit patients in the future. "

Maxwell Wang, Chief Executive Officer of IASO Bio, said, "We are very glad that our high-quality clinical data are presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress, one of the top global academic conferences. It’s also the only oral presentation on a China-developed BCMA CAR-T treatment at this year’s EHA (Free EHA Whitepaper) Congress. The updated data reinforce the advantages and uniqueness of CT103A in the treatment of patients with relapsed/refractory multiple myeloma. Particularly, we enrolled 8 patients with extramedullary multiple myeloma and 10 patients receiving prior murine BCMA CAR-T treatment. All patients have obtained clinical benefits. IASO Biotherapeutics will continue to leverage its innovative clinical development strategy to further prove the advantages of CT103A. We also look forward to the oral presentation by Professor Chunrui Li with Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology (HUST) at the EHA (Free EHA Whitepaper) Congress."

Presentation details:

Abstract: S194 AN UPDATED PHASE 1 STUDY OF A NOVEL FULLY HUMAN BCMA-TARGETING CAR-T CELLS (CT103A) IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA

Type: Oral Presentation

Session title: T cell re-directing therapies in relapsed/refractory multiple myeloma

About Multiple Myeloma

Multiple Myeloma is a deadly blood cancer that often infiltrates the bone marrow causing anemia, kidney failure, immune problems, and bone fractures. For multiple myeloma patients, common first-line drug treatments include proteasome inhibitors, immunomodulatory drugs, and alkylating agents. While treatment may result in remission, most patients will inevitably enter the relapsed or refractory stage as there’s currently no cure. As a result, there is a significant unmet need for patients with relapsed/refractory multiple myeloma.

About IBI326 (BCMA CAR-T)

IBI326 is an innovative therapy co-developed by Innovent and IASO Bio. Previous studies indicate subjects with relapsed/refractory multiple myeloma (R/R MM) who received high-dose BCMA-targeting CAR-T cells may achieve better remission but have worse adverse events. Moreover, once the disease progresses again, the re-infusion of CAR-T cells will not be effective. To solve this dilemma, IBI326 has been developed, a lentiviral vector containing a CAR structure with a fully human scFv, CD8a hinger and transmembrane, 4-1BB co-stimulatory and CD3ζ activation domains. Based on strict selection and screening, utilizing a proprietary in-house optimization platform, the construct of the BCMA CAR-T is potent and persistent. In February 2021, IBI326 was granted breakthrough therapy designation by the NMPA for the treatment of relapsed/refractory multiple myeloma.