2seventy bio (TSVT) Provides Company Outlook for 2023

2seventy bio, Inc. (Nasdaq: TSVT) announced today key corporate milestones and financial outlook for 2023.

“2022 was the launch year of 2seventy bio and we made important progress establishing the fundamentals of our business,” said Nick Leschly, chief kairos officer. “We focused on bringing Abecma, our first-in-class BCMA CAR T for multiple myeloma, to as many patients in need as possible. Together with BMS, we made significant progress in scaling our manufacturing capacity as well as delivering positive data from our KarMMa-3 study almost one year ahead of schedule. In 2023, our goals include expanding the Abecma label, launching a study of Abecma in newly diagnosed patients, and continuing to increase our manufacturing capacity to drive toward the potential $2-3B U.S. peak sales opportunity. In 2022, we also were able to double down on our differentiated cell therapy science and translational platform to more fully unleash the curative potential of the T cell. On this dimension, we initiated enrollment on two first of kind clinical studies in B-NHL and AML with data expected throughout 2023. We also advanced several solid tumor programs toward the clinic and expanded our translational plans with Regeneron. Importantly, we are nearing completion of our 270-MPH in-house clinical drug product manufacturing site adding to our relationship with JW Therapeutics to accelerate clinical product development in China and more effectively support our growing U.S. clinical needs. Finally, we set a strong people and culture foundation that is passionately committed to finding a way to give back priceless time to the patients and families we serve.”

Abecma Outlook
Commercial Performance and Manufacturing Progress
Commercial demand for Abecma (idecabtagene vicleucel) remained strong throughout 2022. 2seventy bio and BMS increased manufacturing capacity and made important progress on key supply chain metrics, including delivering drug product at an average in-spec rate of 85-90% with a turnaround time (time from patient apheresis to delivery of Abecma) of approximately 30 days. As previously stated, 2seventy bio anticipates reaching the upper end of $250-$300M for topline U.S. revenue in 2022.

In 2023, the company anticipates continued increases in vector and drug product manufacturing capacity, including an additional adherent vector manufacturing suite, enabling topline U.S. revenue of $470-$570M. Looking out into 2024-25, 2seventy bio expects further commercial growth with an anticipated label expansion. With this growth, 2seventy bio expects Abecma to generate $200-300M in operating income for 2seventy bio in the 2024-25 period.

KarMMa-3 Results and Regulatory Plans
In August 2022, BMS and 2seventy bio disclosed that KarMMa-3, a Phase 3 study comparing Abecma to standard combination regimens in adults with multiple myeloma that is relapsed and refractory after two to four prior lines of therapy and refractory to the last regimen, had met its primary endpoint. Results of a pre-specified interim analysis showed that KarMMa-3 met its primary endpoint of demonstrating a statistically significant improvement in progression-free survival. Treatment with Abecma also showed an improvement in the key secondary endpoint of overall response rate compared to standard regimens. Follow-up for overall survival, a key secondary endpoint, remains ongoing.

The full data from this study will be presented at the EBMT-EHA 5th European CAR T-cell meeting in Rotterdam (Netherlands) on February 10, 2023. Abstracts for this meeting are currently available on the conference website. Based on the positive data, the companies anticipate submitting a supplemental Biologics Licensing Application (sBLA) to the U.S. FDA in Q1 2023, with potential approval also in 2023.

KarMMa-2 Results and Planned Study in Newly Diagnosed Multiple Myeloma
At ASH 2022, BMS and 2seventy bio presented data from two arms of the KarMMa-2 study. These data suggest that Abecma can provide significant clinical benefit to patients with suboptimal response to transplant and support further evaluation of Abecma in newly diagnosed patients in the KarMMa-9 study, with planned study initiation in 2023.

The KarMMa-9 study is anticipated to enroll patients with newly diagnosed multiple myeloma who have suboptimal response to transplant, which represents a patient population with an unfavorable outcome. Of the approximately 70% of newly diagnosed multiple myeloma patients who are eligible and chose to receive transplant, up to 50% do not achieve complete response post-transplant, underscoring the high unmet need in this population.

Next-Gen Cell Therapy Product Engine and Pipeline
Pipeline Programs Update

• bbT369: In 2022, 2seventy bio made meaningful progress in enrolling patients with relapsed and/or refractory B cell non-Hodgkin lymphoma (B-NHL) in its Phase I CRC-403 study of bbT369, an investigational novel CD79a/CD20 dual-targeting CBLB gene edited CAR T cell therapy. At the end of 2022, 2seventy bio completed the first cohort of dose-escalation. There were no dose-limiting toxicities observed to-date. The manufacturing success rate was high and turnaround time was in line with other autologous CAR Ts despite the additional complexity of this product. Patient enrollment in CRC-403 continues at the second dose level, and 2seventy bio anticipates sharing a data update in 2023.
• SC-DARIC33: 2seventy bio and Seattle Children’s Research Institute (SCRI) is nearing completion of the mandatory adult dosing phase of a Phase 1 study evaluating our rapamycin-regulated CAR T cell therapy in patients with acute myeloid leukemia (AML); the totality of the initial data to-date suggests SC-DARIC33 activation by rapamycin. Patient enrollment in PLAT-08 continues, and, with SCRI, we expect to present initial clinical data in 2023. Additionally, a next-generation AML product concept has been selected and will enter non-clinical development in 2023. This new candidate is built off of our new RESET receptor architecture and incorporates dual targeting along with a potency enhancement while retaining the DARIC-like drug-regulation.
• MUC16: In collaboration with Regeneron, we anticipate an Investigational New Drug application in 2023 for our CAR T targeting MUC16 in patients with relapsed/refractory ovarian cancer. This first-in-human study will prospectively include combination agents, including those in Regeneron’s pipeline, and will be the first program to utilize 2seventy bio’s new in-house drug product manufacturing facility.
• MAGE-A4: In 2022, 2seventy bio entered into an agreement with JW Therapeutics to clinically evaluate 2seventy bio’s potency enhanced MAGE-A4 TCR program in solid tumors which is being developed as part of a collaboration with Regeneron. MAGE-A4 is a member of the MAGE family of cancer-testis antigens expressed in a number of solid tumor types. JW Therapeutics plans an investigator-initiated trial in China in 2023, initially focused on esophageal carcinoma.

Regeneron Collaboration Amendment
Last week, 2seventy bio announced an expanded translational collaboration with Regeneron to facilitate the acceleration of novel cell therapy-based combinations for solid tumors. The collaboration will leverage 2seventy bio’s unique cell therapy engineering and early-stage development capabilities, including the newly built in-house clinical cell therapy manufacturing facility, with Regeneron’s differentiated antibodies and bispecifics.

To support this expanded clinical development plan Regeneron made a $20 million equity investment in 2seventy bio at a 50% premium and has committed to another $20 million in near-term pre-clinical and clinical milestones. The parties will continue sharing costs for these activities in a manner largely consistent with the existing agreement, with Regeneron covering 75% of certain preclinical costs necessary to study combinations and 100% of the costs for the arms of the clinical studies that include Regeneron agents through regulatory approval. For other programs, cost-sharing will follow the existing 50/50 cost sharing agreement.

Preliminary 2023 Financial Outlook
2seventy bio entered 2023 with approximately $268M in cash, cash equivalents and marketable securities and incurred net cash spend of approximately $260M in 2022, driven in part by upfront investments in Abecma manufacturing. In early January 2023, the Company received a $20M equity investment as part of its expanded Regeneron collaboration resulting in a cash balance of approximately $288M at the start of 2023. Based on its current operating plan, 2seventy bio anticipates net cash spend of $180 – 220M in 2023 and expects net cash spend to be meaningfully lower in 2024 due to the projected continued U.S. Abecma commercial ramp and improving profitability. The range on Abecma revenue guidance for 2023 and Abecma cash flow in 2024 and 2025 reflects the variability in timing of regulatory approvals for vector and drug product capacity increases. Our base case operating plan assumes continued success in vector and drug product scale up for Abecma and under this plan, the Company anticipates that its cash will be sufficient to fund current planned operations into early 2025.

“In addition to scientific innovation and patient focus, we are 2x focused on building a cell therapy company that is fit for purpose with a path to financial sustainability,” said Chip Baird, chief financial officer. “Our 2022 net cash spend of approximately $260M was impacted by significant upfront investments in Abecma manufacturing that made the year our high-water mark in terms of our annual net cash spend. Looking forward, we see Abecma contributing cash back to the business in 2023, with significant growth in Abecma cash flow in 2024-25. Over the next three years, we plan to maximize the cash flow from the Abecma business, carefully manage expenses, and look to continue to be active on the corporate development front to deliver transformative medicines to the patients we serve while generating value for our shareholders.”

Updated Corporate Presentation
These updates and additional information can be found in the company’s updated corporate presentation, which can be found in the investor section of www.2seventybio.com.

About bbT369
bbT369 is an investigational dual-targeting CAR T cell therapy with a gene edit being evaluated for the treatment of patients with relapsed and/or refractory B-NHL. In the 3L+ relapsed and/or refractory B-NHL setting, 60-70% of patients treated with commercially available CAR T cell therapies do not achieve a long-term remission, highlighting a significant unmet clinical need.

To address this unmet need, bbT369 has been designed with three layers of innovation that aim to address several potential mechanisms of anti-CD19 CAR T cell therapy failure: dual targeting (CD79a/CD20), split co-stimulation signaling technology, and a gene edit to remove the function of CBLB.

In December 2021, the FDA cleared the Investigational New Drug (IND) application for bbT369.

The clinical development program for bbT369 includes the Phase 1/2 CRC-403 study (NCT05169489). Safety and potential efficacy of bbT369 in patients with specific subtypes of relapsed and/or refractory B-NHL will be assessed, including patients who relapsed after CD19 CAR T cell therapy as well as patients who are CAR-naïve.

bbT369 is not approved for any indication in any geography.

About SC-DARIC33
SC-DARIC33 is an investigational CD33-specific cell therapy that utilizes 2seventy bio’s proprietary Dimerizing Agent Regulated Immunoreceptor Complex (DARIC) T cell platform. SC-DARIC33 is designed as a regulatable, potentially first-in-class autologous T cell therapy and is now being studied at Seattle Children’s in a Phase 1 trial, PLAT-08 (NCT05105152), as a first-in-human investigation of the DARIC T cell platform in relapsed/refractory pediatric and young adult AML.

DARIC separates the antigen binding and signaling functions of a CAR, with the intent that these two components are brought together by the small molecule rapamycin (RAPA), resulting in a functional CAR construct. In preclinical studies, SC-DARIC33 has shown robust drug-dependent anti-tumor activity (similar to CD19 CAR T controls). Importantly, SC-DARIC33 has been shown to be activated by low non-immunosuppressive concentrations of RAPA in the blood and, when RAPA is removed, DARIC returns to an inactive state. SC-DARIC33 tests the hypothesis that a pharmacologically regulated CAR can enable potent AML targeting while limiting toxicities associated with normal myeloid and myeloid progenitor cell targeting.

The investigation of SC-DARIC33 in the Phase 1 PLAT-08 study of pediatric and young adult AML patients and the scientific translation of these data are intended to establish the safety profile of SC-DARIC33 and evaluate feasibility of the reversable modulation (OFF-ON-OFF) of SC-DARIC33.

You May Also Be Interested In

• Trump highlights ibogaine development push, Psyence BioMed responds
• Interactive Brokers adds SafetyPay funding for Latin America clients
• BT Brands posts Q2 profit, cuts costs as restaurant sales dip