GlobeNewswire by notified

Novartis announces T-Charge™, next-generation CAR-T platform with first-in-human data at ASH 2021

Share
  • T-Charge, a next-generation platform that aims to revolutionize CAR-T cell therapy, will serve as foundation for various investigational CAR-T therapies
  • Early data from first-in-human dose-escalation trials with YTB323 and PHE885 show promising results that support ongoing research and development with the hope of improving upon existing CAR-T therapies1,2
  • Initial efficacy results include 73% complete response rate at month three with dose level two in the YTB323 study in DLBCL and 100% best overall response in the PHE885 study in multiple myeloma1,2
  • Novartis continues to accelerate development of the T-Charge platform, which preserves T cell stemness, an important characteristic closely tied to its therapeutic potential, and implements important process efficiencies3,4
  • With the implementation of important process efficiencies, the T-Charge platform will be rapid, compared with traditional CAR-T, and reliable, through simplified processes and streamlined quality control1-4

Basel, December 13, 2021 — Novartis today announced the introduction of T-Charge™, the company’s next-generation CAR-T platform that will serve as the foundation for various new investigational CAR-T cell therapies in the Novartis pipeline. At the 63rd American Society of Hematology Annual Meeting & Exposition (ASH) 2021, Novartis will present early clinical data from ongoing Phase I clinical trials with YTB323 (anti-CD19) and PHE885 (anti-BCMA), the first Novartis CAR-T cell therapies developed using this platform. Notably, initial efficacy data show a complete response rate of 73% (95% CI: 44.9, 92.2) at month three for the 15 patients with diffuse large B-cell lymphoma (DLBCL) who received dose level two of YTB3231. For the 11 patients with multiple myeloma who received the two highest doses of PHE885, the best overall response was 100%2.

The T-Charge platform preserves T cell stemness, the ability to self-renew and mature, which results in a product containing greater proliferative potential and fewer exhausted T cells3,4. With T-Charge, CAR-T cell expansion occurs primarily within a patient’s body (in-vivo), eliminating the need for an extended culture time outside of the body (ex-vivo)3,4. These unique characteristics of the T-Charge platform may lead to better and more durable responses, improved long-term outcomes and a reduced risk of severe adverse events1-4.

“With T-Charge, we aim to build on the vast knowledge gleaned from early investment in CAR-T research and trials. Our ambition now is to go beyond incremental advances, to further reimagine CAR-T cell therapy and give patients a higher likelihood of durable responses with the ultimate potential for a cure,” said Jay Bradner, President of the Novartis Institutes for BioMedical Research. “We are encouraged by these promising early clinical data from the first CAR-T cell therapies produced using the T-Charge platform as we look to accelerate their development and delivery to patients.”

Phase I YTB323 clinical study1
YTB323, an investigational, autologous CD19-directed CAR-T cell therapy developed using the T-Charge platform, showed promising results in the diffuse large B-cell lymphoma arm of a first-in-human, multicenter, Phase I dose-escalation study. Patients received a single treatment of YTB323 at two dose levels (DL). The median administered doses were 2.5×106 CAR+ cells (DL1; n=4) and 12.5×106 CAR+ cells (DL2; n=16). Of the 15 patients who received YTB323 treatment at DL2 at least three months prior to the data cut-off, the complete response (CR) rate was 73% (95% CI: 44.9, 92.2), including two patients who were in CR prior to treatment with YTB323.

For the 20 patients evaluable for safety, there were no new safety signals beyond those previously known to be related to CD19-directed CAR-T cell therapy. All AEs were reported regardless of the study drug relationship. Six patients experienced CRS including five of grade 1/2 and one of grade 4. Five patients had neurological adverse reactions (AR), of which two events were considered serious (both at DL2; one experienced grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) and the other experienced grade 2 seizure that resulted in a grade 3 ICANS). Recruitment for this trial is ongoing. These data will be presented in an oral session at the ASH annual meeting (Abstract #740; Monday, December 13, 3:00 PM EST).

“The introduction of CAR-T cell therapy led to unprecedented efficacy results for patients facing limited treatment options and a poor prognosis. Unfortunately, some patients with late-stage B-cell malignancies relapse or do not respond after initial response when treated with traditional CAR-T cell therapies,” said principal investigator Ian W. Flinn, MD, PhD, Director of the Lymphoma Research Program at Sarah Cannon Research Institute in Nashville. “As part of a community of researchers, physicians and patient advocates, I am hopeful about the promise of novel and next-generation CAR-T cell therapies.”

Phase I PHE885 clinical study2
PHE885, an investigational, autologous BCMA-directed CAR-T cell therapy developed using the T-Charge platform, demonstrated promising results in patients with relapsed or refractory multiple myeloma in a first-in-human Phase I, multicenter, dose-escalation study. Fifteen patients were evaluated for efficacy and safety and the fixed doses received were 2.5×106 (n=4), 5×106 (n=10) and 14.3×106 CAR-T cells (n=1). Although the follow-up period was brief, PHE885 shows encouraging initial clinical activity with a best overall response of 100% for patients receiving the 5×106 or 14.3×106 CAR-T cell dose, with responses deepening over time. With a median follow-up of 3.5 months, eight of 15 patients had ongoing responses at the time of data cutoff. Of the evaluable patients at three months post administration, 34% (2/6) were MRD-negative by next-generation sequencing (NGS) at 10-6; 43% (3/7) were MRD-negative at 10-5.

All patients experienced CRS with two patients experiencing grade ≥3 CRS. No patients experienced grade 4 or 5 CRS. All neurotoxicity events (n=4) were nonserious, grade 1-2, reversible, and temporally associated with CRS. Recruitment for this trial is ongoing. These data will be presented in a poster presentation session at the ASH annual meeting (Abstract #3864; Monday, December 13, 6:00 PM EST).

Results from pre-clinical studies of YTB323 and PHE885 that served as the scientific rationale to initiate these Phase I clinical trials will also be presented at the meeting (Abstracts #2848 and #2770).

About T-Charge™1-4
T-Charge is a next-generation CAR-T platform, innovated at the Novartis Institutes for BioMedical Research (NIBR), that will serve as the foundation for various new investigational CAR-T cell therapies in the Novartis pipeline. By implementing the T-Charge platform, we aim to revolutionize CAR-T cell therapy with new products that have the potential to offer patients a higher likelihood of better and more durable responses, improved long-term outcomes and a reduced risk of severe adverse events. The T-Charge platform preserves T cell stemness (T cell ability to self-renew and mature), an important T cell characteristic closely tied to its therapeutic potential, which results in a product containing greater proliferative potential and fewer exhausted T cells. With T-Charge, CAR-T cell expansion occurs primarily within the patient’s body (in-vivo), eliminating the need for an extended culture time outside of the body (ex-vivo). The T-Charge platform, which implements important process efficiencies, will be rapid, compared with traditional CAR-T, and reliable, through simplified processes and streamlined quality control. Multiple CAR-T therapies, including YTB323 and PHE885, are being developed using the Novartis T-Charge platform.

About Novartis commitment to Oncology Cell Therapy
Novartis has a mission to reimagine medicine by bringing curative cell therapies to patients worldwide. Novartis has a deep CAR-T pipeline and ongoing investment in manufacturing and supply chain process improvements. With active research underway to broaden the impact of cell and gene therapy in oncology, Novartis is going deeper in hematological malignancies, reaching patients with other cancer types and evaluating next-generation CAR-T cell therapies that focus on new targets and utilize new platforms.

Novartis was the first pharmaceutical company to significantly invest in pioneering CAR-T research and initiate global CAR-T trials.

Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “seek,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis
Novartis is reimagining medicine to improve and extend people’s lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. Novartis products reach nearly 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 108,000 people of more than 140 nationalities work at Novartis around the world. Find out more at https://www.novartis.com.

Novartis is on Twitter. Sign up to follow @Novartis at https://twitter.com/novartisnews
For Novartis multimedia content, please visit https://www.novartis.com/news/media-library
For questions about the site or required registration, please contact media.relations@novartis.com

References

  1. Flinn, I. et al. A First-in-Human Study of YTB323, a Novel, Autologous CD19-Directed CAR-T Cell Therapy Manufactured Using the Novel T-Charge platform, for the Treatment of Patients (Pts) with Relapsed/Refractory (r/r) Diffuse Large B-Cell Lymphoma (DLBCL). Oral Presentation #740. 2021 American Society of Hematology (ASH) Annual Meeting, Dec 11-14, Atlanta, GA and Virtual.
  2. Sperling, A. et al. Phase I Study of PHE885, a Fully Human BCMA-Directed CAR-T Cell Therapy for Relapsed/Refractory Multiple Myeloma Manufactured in<2 days Using the T-Charge. Poster #3864. 2021 American Society of Hematology (ASH) Annual Meeting, Dec 11-14, Atlanta, GA and Virtual.
  3. Engels, B. et al. Preservation of T-Cell Stemness with a Novel Expansionless CAR-T Manufacturing Process, Which Reduces Manufacturing Time to Less Than Two Days, Drives Enhanced CAR-T Cell Efficacy. Abstract #2848. 2021 American Society of Hematology (ASH) Annual Meeting, Dec 11-14, Atlanta, GA and Virtual.
  4. Bu, D. et al. Identification and Development of PHE885: A Novel and Highly Potent Fully Human Anti-BCMA CAR-T Manufactured with a Novel T-Charge Platform for the Treatment of Multiple Myeloma. Abstract #2770. 2021 American Society of Hematology (ASH) Annual Meeting, Dec 11-14, Atlanta, GA and Virtual.

# # #

Novartis Media Relations
E-mail: media.relations@novartis.com

Anja von Treskow
Novartis External Communications
+41 79 392 8697 (mobile)
anja.von_treskow@novartis.com



Julie Masow
Novartis US External Communications
+1 862 579 8456
julie.masow@novartis.com
Fiona Phillips
Novartis Oncology Communications
+1 862 217 9396
fiona.phillips@novartis.com

Novartis Investor Relations
Central investor relations line: +41 61 324 7944
E-mail: investor.relations@novartis.com

CentralNorth America
Samir Shah+41 61 324 7944Sloan Simpson+1 862 345 4440
Thomas Hungerbuehler+41 61 324 8425Alina Levchuk+1 862 778 3372
Isabella Zinck+41 61 324 7188Parag Mahanti+1 973-876-4912
To view this piece of content from www.globenewswire.com, please give your consent at the top of this page.
To view this piece of content from ml-eu.globenewswire.com, please give your consent at the top of this page.

About GlobeNewswire by notified

GlobeNewswire by notified
GlobeNewswire by notified
One Liberty Plaza - 165 Broadway
NY 10006 New York

https://notified.com

GlobeNewswire by notified is one of the world's largest newswire distribution networks, specializing in the delivery of corporate press releases financial disclosures and multimedia content to the media, investment community, individual investors and the general public.

Subscribe to releases from GlobeNewswire by notified

Subscribe to all the latest releases from GlobeNewswire by notified by registering your e-mail address below. You can unsubscribe at any time.

Latest releases from GlobeNewswire by notified

Nordic American Tankers Ltd (NYSE: NAT) – Further Purchase of NAT shares by Board Member Alexander Hansson21.1.2022 16:32:14 CET | Press release

Friday, January 21, 2022 Dear Shareholders and Investors, Alexander Hansson, Board Member in Nordic American Tankers Ltd (NAT) and son of Herbjorn Hansson, the NAT Founder, Chairman and CEO, has today bought 50,000 shares in NAT at $ 1.557 per share. Following the transaction, Alexander Hansson privately owns 1,185,000 shares in NAT. As in the past, the Hansson family is the largest private shareholder in the company. Alexander Hansson commented: "I strongly believe in the future of NAT" Sincerely, Herbjorn Hansson Founder, Chairman & CEO Nordic American Tankers Ltd. www.nat.bm CAUTIONARY STATEMENT REGARDING FORWARD-LOOKING STATEMENTS Matters discussed in this press release may constitute forward-looking statements. The Private Securities Litigation Reform Act of 1995 provides safe harbor protections for forward-looking statements in order to encourage companies to provide prospective information about their business. Forward-looking statements include statements concerning plans, obje

CONDITIONS FOR RIKSBANK REVERSED AUCTIONS SEK TREASURY BILLS21.1.2022 16:20:00 CET | Press release

Bid procedure, 2022-01-26BillsSWEDISH T-BILL: SE0017232689. 2022-04-20 Bid date2022-01-26Bid times10.00-11.00 (CET/CEST) on the Bid dateRequested volume (corresponding nominal amount)SE0017232689: 2000 mln SEK +/-1000 mln SEK Highest permitted bid volume (corresponding nominal amount)SE0017232689: 2000 mln SEK per bid Lowest permitted bid volume (corresponding nominal amount)SEK 50 million per bidExpected allocation timeNot later than 11.15 (CET/CEST) on the Bid dateDelivery and payment date2022-01-28Delivery of billsTo the Riksbank's account in Euroclear Sweden AB's securities settlement system 1 4948 6383 Stockholm, 2022-01-21 This is a translation of the special terms and conditions published on www.riksbank.se. In the case of any inconsistency between the English translation and the Swedish language version, the Swedish language version shall prevail. Complete terms and conditions can be retrieved at www.riksbank.se.

CONDITIONS FOR RIKSBANK BID PROCEDURE KOMMUNINVEST BONDS21.1.2022 16:20:00 CET | Press release

Bid procedure, 2022-01-25BondsKOMMUNINVEST I SVERIGE: 2311. SE0010948240. 2023-11-13 KOMMUNINVEST I SVERIGE: 2611, SE0012569572, 2026-11-12 KOMMUNINVEST I SVERIGE: 2805, SE0015660139, 2028-05-12 BidsBids on interest and volume are entered via Bloomberg Bond Auction SystemBid date2022-01-25Bid times10.00-11.00Requested volume (corresponding nominal amount)2311: 500 mln SEK +/-250 mln SEK 2611: 500 mln SEK +/-250 mln SEK 2805: 500 mln SEK +/-250 mln SEK Highest permitted bid volume (corresponding nominal amount)2311: 500 mln SEK per bid 2611: 500 mln SEK per bid 2805: 500 mln SEK per bid Lowest permitted bid volume (corresponding nominal amount)SEK 50 million per bidExpected allocation timeNot later than 11.15 (CET/CEST) on the Bid dateDelivery and payment date2022-01-27Delivery of bondsTo the Riksbank's account in Euroclear Sweden AB's securities settlement system 1 4948 6383General Terms and ConditionsGeneral Terms and Conditions General Terms and Conditions för the Riksbank’s Purchase

CONDITIONS FOR RIKSBANK REVERSED AUCTIONS SEK GOVERNMENT BONDS21.1.2022 16:20:00 CET | Press release

Bid procedure, 2022-01-28BondsSWEDEN I/L BOND: 3109. SE0005703550. 2025-06-01 SWEDEN I/L BOND: 3114, SE0013748258, 2030-06-01 Bid date2022-01-28Bid times09.00-10.00 (CET/CEST) on the Bid dateRequested volume (corresponding nominal amount)3109: 500 mln SEK +/-250 mln SEK 3114: 500 mln SEK +/-250 mln SEK Highest permitted bid volume (corresponding nominal amount)3109: 500 mln SEK per bid 3114: 500 mln SEK per bid Lowest permitted bid volume (corresponding nominal amount)SEK 50 million per bidExpected allocation timeNot later than 10.15 (CET/CEST) on the Bid dateDelivery and payment date2022-02-01Delivery of bondsTo the Riksbank's account in Euroclear Sweden AB's securities settlement system 1 4948 6383 Stockholm, 2022-01-21 This is a translation of the special terms and conditions published on www.riksbank.se. In the case of any inconsistency between the English translation and the Swedish language version, the Swedish language version shall prevail. Complete terms and conditions can be

Avance Gas Holding Ltd - Enter into Time Charter Agreement for Avance Capella21.1.2022 14:33:03 CET | Press release

Bermuda, 21 January 2022 - Avance Gas Holding Ltd ("AGAS" or the "Company") announce that we have entered into a Time Charter Agreement for a period of 2 years for our second dual fuel VLGC, Avance Capella, to LPG & Ethylene Shipowner and LPG trader, Petredec. The vessel will commence the time charter shortly after delivery ex-yard in South Korea end of February 2022 and the time charter hire has a mechanism which gives both parties exposure to the spot market rate. This transaction is another step in executing on our strategy to increase our time charter portfolio while also maintaining access to the market upside. For further queries, please contact: Kristian Sørensen, CEO Tel: +47 22 00 48 00 Randi Navdal Bekkelund, CFO Tel: +47 22 00 48 00 About Avance Gas: Avance Gas operates in the global market for transportation of liquefied petroleum gas (LPG). The Company is one of the world's leading owners and operators of very large gas carrier (VLGC) and operates a fleet of thirteen ships

Proposals by the Nomination Board to the Annual General Meeting 2022 of Suominen21.1.2022 13:00:00 CET | Press release

Suominen Corporation's stock exchange release on January 21, 2022 at 2:00 p.m. EET Proposal on the number of the members, on the composition, and on the Chair of the Board of Directors The Nomination Board of Suominen Corporation’s shareholders proposes to the Annual General Meeting that the number of Board members remains unchanged and would be six (6). The Nomination Board proposes to the Annual General Meeting that Andreas Ahlström, Björn Borgman, Jaakko Eskola, Nina Linander and Laura Raitio would be re-elected as members of Suominen Corporation’s Board of Directors. Out of the current Board members, Sari Pajari-Sederholm has informed that she is not available as a candidate for the Board of Directors. In addition, the Nomination Board proposes that Aaron Barsness would be elected as a new member of the Board of Directors. Mr. Aaron Barsness (born 1973, BA (Biology and Environmental Studies), U.S. and Swedish citizen) currently works as the CMO of Fazer Group. He has held a number

Auriant Mining AB (publ.) publishes 12m 2021 operational update21.1.2022 11:20:00 CET | Press release

Highlights: In 12m 2021, total gold production amounted to 910.8 kg (29,283 oz), compared to 964.7 kg (31,014 oz) in 12m 2020, a decrease of 6%, or 53.9 kg (1,731 oz), but in line with the 2021 production plan; Hard rock gold production was 893.3 kg (28,720 oz), compared to 952.7 kg (30,629 oz) in 12m 2020, a decrease of 6%, or 59.4 kg (1,909 oz);Alluvial gold production amounted to 17.5 kg (563 oz), compared to 12.0 kg (386 oz) in 2020, an increase of 46%, or 5,5 kg (178 oz);12m 2021, total gold sales were 818.5 kg (26,316 oz), compared to 946.4 kg (30,428 oz) in 12m 2020, a decrease of 127.9 kg (4,112 oz), or 14%;428,300 tonnes of ore were processed with an average grade of 2.30 g/t;In 12m of 2021, the CIL plant operated for 8,004 hours at an increased throughput rate of 53.5 tonnes per working hour (>50 t/hour) and at the targeted recovery rate of 91.2%;458,500 tonnes of ore were mined in 12m 2021, compared to 387,200 tonnes in 12m 2020, an increase of 71,300 tonnes or 18%. Strippin