UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of
the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): May 8, 2024
(Exact name of registrant as specified in its charter)
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(617 ) 923-1400
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N/A
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
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Item 2.02 Results of Operations and Financial Condition.
On May 8, 2024, Cartesian Therapeutics, Inc. (the “Company”) announced its financial results for the quarter ended March 31, 2024. The full text of the press release issued in connection with the announcement is furnished as Exhibit 99.1 to this Current Report on Form 8-K.
Item 7.01. Regulation FD Disclosure.
The Company from time to time presents and/or distributes to the investment community at various industry and other conferences slide presentations to provide updates and summaries of its business. A copy of its current corporate slide presentation is attached to this Current Report on Form 8-K as Exhibit 99.2.
The information in Items 2.02 and 7.01 of this Form 8-K, including Exhibits 99.1 and 99.2 attached hereto, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.2, except as required by law.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
| Exhibit No. | Exhibit Description | |||||||
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |||||||
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| CARTESIAN THERAPEUTICS, INC. | ||||||||
| Date: May 8, 2024 | By: | /s/ Carsten Brunn, Ph.D. | ||||||
| Carsten Brunn, Ph.D. | ||||||||
| President and Chief Executive Officer | ||||||||
Exhibit 99.1
Cartesian Therapeutics Reports First Quarter 2024 Financial Results and Provides Business Update
Topline data from Phase 2b trial of Descartes-08, the Company’s potential first-in-class mRNA CAR-T cell therapy, in myasthenia gravis on track for mid-2024
On track to dose first patient in Phase 2 trial of Descartes-08 in SLE in 2Q24, as well as Phase 2 basket studies in additional autoimmune indications in 2H24
New headquarters expected to support scale of wholly owned, in-house cGMP manufacturing capabilities for clinical and commercial supply of Company’s pipeline of mRNA cell therapy product candidates
Approximately $104.8M of cash, cash equivalents, and restricted cash as of March 31, 2024, expected to support planned operations into 2H 2026
GAITHERSBURG, MD, May 8, 2024 (GLOBE NEWSWIRE) – Cartesian Therapeutics, Inc. (NASDAQ: RNAC) (the “Company”), a clinical-stage biotechnology company pioneering mRNA cell therapy for autoimmune diseases, today reported financial results for the first quarter ended March 31, 2024, and recent corporate updates.
“We continue to make meaningful progress advancing our innovative pipeline of product candidates and remain on track to report topline results from the Phase 2b trial of our lead product candidate, Descartes-08 for MG, in mid-2024,” said Carsten Brunn, Ph.D., President and Chief Executive Officer of Cartesian. “Looking ahead, we also expect to commence dosing in our Phase 2 trial of Descartes-08 in patients with SLE by the end of the second quarter. Descartes-08 is designed with our novel mRNA-engineered CAR-T technology, is not expected to require preconditioning chemotherapy, and is intended to be administered in an outpatient setting. We remain confident Descartes-08 has the potential to expand the reach of cell therapy to patients with autoimmune diseases and serve as the first CAR-T cell therapy for the treatment of autoimmunity.”
Dr. Brunn continued, “Additionally, we were excited to announce plans to transition to new corporate headquarters in Frederick, Maryland, that will provide us with the infrastructure to support our next phase of growth. We expect this new facility will allow us to scale our wholly owned, in-house cGMP manufacturing capabilities for late-stage clinical and commercial supply of our mRNA cell therapy product candidates, while continuing to maintain control over product quality and production.”
Recent Pipeline Progress and Anticipated Milestones
Descartes-08 for Myasthenia Gravis (MG)
•Topline data from randomized Phase 2b trial in patients with MG on track for mid-2024.
•Recently granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of MG.
•Previously disclosed positive, long-term follow-up results from Phase 2a trial. In April 2024, the Company announced that these data will be featured in an oral presentation at the American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting on May 10, 2024 in Baltimore, Maryland.
•Descartes-08, the Company’s lead product candidate, is an autologous anti-B cell maturation antigen (BCMA) mRNA-engineered chimeric antigen receptor T-cell therapy (mRNA CAR-T).
Descartes-08 for Systemic Lupus Erythematosus (SLE)
•Dosing of first patient in Phase 2 trial of Descartes-08 in patients with SLE expected in second quarter of 2024.
•The Phase 2 trial is designed to assess the safety and tolerability of outpatient Descartes-08 administration without preconditioning chemotherapy.
•SLE is an incurable autoimmune disease marked by systemic inflammation that affects multiple organ systems and impacts approximately 1.5 million people in the United States.
Descartes-15 for Multiple Myeloma
•Planning for the first-in-human Phase 1 dose escalation trial is underway to assess the safety and tolerability of outpatient Descartes-15 administration in patients with multiple myeloma.
•Descartes-15 is a next-generation autologous anti-BCMA mRNA CAR-T product candidate designed to have predictable and controllable pharmacokinetics, potentially circumventing preconditioning chemotherapy, and avoiding the risk of genomic integration.
•The Company expects to subsequently assess Descartes-15 in autoimmune indications.
Corporate Updates
Preferred Stock Conversion and Reverse Stock Split Approved at Special Meeting of Stockholders
•In March 2024, Cartesian announced the approval for the conversion of the Company’s Series A Non-Voting Convertible Preferred Stock into the Company’s common stock and a 1-for-30 reverse stock split of the Company’s common stock.
•Following the reverse stock split and the automatic conversion of the Company’s Series A Non-Voting Convertible Preferred Stock into common stock, the number of issued and outstanding shares of the Company’s common stock is approximately 17.8 million shares.
Transitioning Corporate Headquarters to Frederick, Maryland
•In March 2024, the Company announced plans to transition its corporate headquarters to Frederick, Maryland. Following this announcement, Cartesian further expanded the footprint of this facility by approximately 30% through an amended agreement.
•The Company now has approximately 27,000 square feet of state-of-the-art current good manufacturing practice (cGMP) compliant manufacturing and laboratory space, as well as general and administrative office space to support the Company’s continued growth. This facility reinforces the development of Cartesian’s clinical and preclinical programs through clinical and commercial manufacturing scale capabilities and advanced research and development laboratory space.
•By conducting all manufacturing in-house, Cartesian expects to optimize processes more rapidly and iteratively while directly working to ensure adherence to strict quality standards. The Company believes this facility will facilitate production of potent yet safer, cost-effective mRNA cell therapy product candidates for late-stage clinical and commercial supply.
First Quarter 2024 Financial Results
•Cash, cash equivalents, and restricted cash of approximately $104.8 million as of March 31, 2024. The Company’s cash, cash equivalents and restricted cash as of March 31, 2024 is expected to support planned operations and the development of Cartesian’s pipeline into the second half of 2026, including the planned Phase 3 trial of Descartes-08 in MG.
•Research and development expenses were $9.7 million for the quarter ended March 31, 2024, compared to $18.6 million for the quarter ended March 31, 2023. The decrease in research and development expenses of $8.9 million for the quarter ended March 31, 2024 was primarily the result of reductions in expenses incurred for preclinical and clinical programs due to the strategic reprioritization in the Company’s clinical pipeline.
•General and administrative expenses were $9.5 million for the quarter ended March 31, 2024, compared to $5.7 million for the quarter ended March 31, 2023. The increase in expense of $3.8 million for the quarter ended March 31, 2024 was primarily due to an increase in professional fees incurred in connection with the Company’s merger in November 2023.
•Net loss was $(56.8) million, or $(10.50) per share (basic/diluted), for the quarter ended March 31, 2024, compared to net loss of $(21.7) million, or $(4.24) per share (basic/diluted), for the quarter ended March 31, 2023.
About Cartesian Therapeutics
Cartesian Therapeutics is a clinical-stage company pioneering mRNA cell therapies for the treatment of autoimmune diseases. The Company’s lead asset, Descartes-08, is a potential first-in-class mRNA CAR-T in Phase 2b clinical development for patients with generalized myasthenia gravis. Additional Phase 2 studies are planned in systemic lupus erythematosus under an allowed IND, as well as basket trials in additional autoimmune indications. The Company’s clinical-stage pipeline also includes Descartes-15, a next-generation, autologous anti-BCMA mRNA CAR-T. For more information, please visit www.cartesiantherapeutics.com or follow the Company on LinkedIn or X, formerly known as Twitter.
Forward Looking Statements
Any statements in this press release about the future expectations, plans and prospects of the Company, including without limitation, statements regarding the Company’s expected cash resources and cash runway, the Company’s estimated cash on hand, the Company’s headquarters relocation, the Company’s manufacturing capabilities and ability to supply necessary quantities of its product candidates for clinical trials and potential commercialization, the Company’s ability to maintain control over its product quality and production, the potential of the Company’s technology to enable precision control and optimization of engineered cells for diverse cell therapies leveraging multiple modalities, the potential of Descartes-08 and Descartes-15 and the Company’s other product candidates to treat myasthenia gravis, systemic lupus erythematosus, or any other disease, the anticipated initiation timing of planned clinical trials, the anticipated timing or the outcome of ongoing and planned clinical trials, studies and data readouts, the anticipated timing or the outcome of the FDA’s review of the Company’s regulatory filings, the Company’s ability to conduct its clinical trials and preclinical studies, the timing or making of any regulatory filings, the anticipated timing or outcome of selection of developmental product candidates, the ability of the Company to consummate any expected agreements and licenses and to realize the anticipated benefits thereof, the novelty of treatment paradigms that the Company is able to develop, the potential of any therapies developed by the Company to fulfill unmet medical needs, the Company’s ability to enter into and maintain its strategic partnerships, and enrollment in the Company’s clinical trials and other statements containing the words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “hypothesize,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including, but not limited to, the following: the uncertainties inherent in the initiation, completion and cost of clinical trials including proof of concept trials, including uncertain outcomes, the availability and timing of data from ongoing and future clinical trials and the results of such trials, whether preliminary results from a particular clinical trial will be predictive of the final results of that trial and whether results of early clinical trials will be indicative of the results of later clinical trials, the ability to predict results of studies performed on human beings based on results of studies performed on non-human subjects, the unproven approach of the Company’s technology, potential delays in enrollment of patients, undesirable side effects of the Company’s product candidates, its reliance on third parties to conduct its clinical trials, the Company’s inability to maintain its existing or future collaborations, licenses or contractual relationships, its inability to protect its proprietary technology and intellectual property, potential delays in regulatory approvals, the availability of funding sufficient for its foreseeable and unforeseeable operating expenses and capital expenditure requirements, the Company’s recurring losses from operations and negative cash flows, substantial fluctuation in the price of the Company’s common stock, risks related to geopolitical conflicts and pandemics and other important factors discussed in the “Risk Factors” section of the Company’s most recent Annual Report on Form 10-K and subsequently filed Quarterly Reports on Form 10-Q, and in other filings that the Company makes with the Securities and Exchange Commission. In addition, any forward-looking statements included in this press release represent the Company’s views only as of the date of its publication and should not be relied upon as representing its views as of any subsequent date. The Company specifically disclaims any intention to update any forward-looking statements included in this press release, except as required by law.
Cartesian Therapeutics, Inc. and Subsidiaries
Consolidated Balance Sheets
(Amounts in thousands, except share data and par value)
| March 31, 2024 | December 31, 2023 | ||||||||||
| (Unaudited) | |||||||||||
| Assets | |||||||||||
| Current assets: | |||||||||||
| Cash and cash equivalents | $ | 103,418 | $ | 76,911 | |||||||
| Accounts receivable | 2,006 | 5,870 | |||||||||
| Unbilled receivables | 2,370 | 2,981 | |||||||||
| Prepaid expenses and other current assets | 3,315 | 4,967 | |||||||||
| Total current assets | 111,109 | 90,729 | |||||||||
| Non-current assets: | |||||||||||
| Property and equipment, net | 2,402 | 2,113 | |||||||||
| Right-of-use asset, net | 9,556 | 10,068 | |||||||||
| In-process research and development assets | 150,600 | 150,600 | |||||||||
| Goodwill | 48,163 | 48,163 | |||||||||
| Long-term restricted cash | 1,377 | 1,377 | |||||||||
| Investments | 2,000 | 2,000 | |||||||||
| Total assets | $ | 325,207 | $ | 305,050 | |||||||
| Liabilities, convertible preferred stock, and stockholders’ deficit | |||||||||||
| Current liabilities: | |||||||||||
| Accounts payable | $ | 2,517 | $ | 3,150 | |||||||
| Accrued expenses and other current liabilities | 9,516 | 15,572 | |||||||||
| Lease liability | 2,229 | 2,166 | |||||||||
| Deferred revenue | 412 | 2,311 | |||||||||
| Warrant liabilities | 597 | 720 | |||||||||
| Contingent value right liability | 21,383 | 15,983 | |||||||||
| Forward contract liabilities | — | 28,307 | |||||||||
| Total current liabilities | 36,654 | 68,209 | |||||||||
| Non-current liabilities: | |||||||||||
| Lease liability, net of current portion | 8,228 | 8,789 | |||||||||
| Deferred revenue, net of current portion | — | 3,538 | |||||||||
| Warrant liabilities, net of current portion | 4,755 | 5,674 | |||||||||
| Contingent value right liability, net of current portion | 376,517 | 342,617 | |||||||||
| Deferred tax liabilities, net | 15,853 | 15,853 | |||||||||
| Total liabilities | 442,007 | 444,680 | |||||||||
Series A Preferred Stock, $0.0001 par value; no and 548,375 shares authorized as of March 31, 2024 and December 31, 2023, respectively; no and 435,120.513 shares issued and outstanding as of March 31, 2024 and December 31, 2023, respectively | — | 296,851 | |||||||||
| Options for Series A Preferred Stock | — | 3,703 | |||||||||
| Stockholders’ deficit: | |||||||||||
Series A Preferred Stock, $0.0001 par value; 548,375 and no shares authorized as of March 31, 2024 and December 31, 2023, respectively; 534,260.839 and no shares issued and outstanding as of March 31, 2024 and December 31, 2023, respectively | — | — | |||||||||
| Preferred stock, $0.0001 par value; 10,000,000 and 9,451,625 shares authorized as of March 31, 2024 and December 31, 2023, respectively; no shares issued and outstanding as of March 31, 2024 and December 31, 2023 | — | — | |||||||||
| Common stock, $0.0001 par value; 350,000,000 shares authorized as of March 31, 2024 and December 31, 2023; 5,515,836 and 5,397,597 shares issued and outstanding as of March 31, 2024 and December 31, 2023, respectively | 1 | 1 | |||||||||
| Additional paid-in capital | 559,275 | 179,062 | |||||||||
| Accumulated deficit | (671,471) | (614,647) | |||||||||
| Accumulated other comprehensive loss | (4,605) | (4,600) | |||||||||
| Total stockholders’ deficit | (116,800) | (440,184) | |||||||||
| Total liabilities, convertible preferred stock, and stockholders’ deficit | $ | 325,207 | $ | 305,050 | |||||||
Cartesian Therapeutics, Inc. and Subsidiaries
Consolidated Statements of Operations and Comprehensive Income (Loss)
(Amounts in thousands, except share and per share data)
| Three Months Ended March 31, | |||||||||||
| 2024 | 2023 | ||||||||||
| (Unaudited) | |||||||||||
| Collaboration and license revenue | $ | 5,840 | $ | 5,938 | |||||||
| Operating expenses: | |||||||||||
| Research and development | 9,738 | 18,624 | |||||||||
| General and administrative | 9,450 | 5,695 | |||||||||
| Total operating expenses | 19,188 | 24,319 | |||||||||
| Operating loss | (13,348) | (18,381) | |||||||||
| Investment income | 1,164 | 1,331 | |||||||||
| Foreign currency transaction, net | — | 19 | |||||||||
| Interest expense | — | (808) | |||||||||
| Change in fair value of warrant liabilities | 1,042 | (4,079) | |||||||||
| Change in fair value of contingent value right liability | (39,300) | — | |||||||||
| Change in fair value of forward contract liabilities | (6,890) | — | |||||||||
| Other income, net | 508 | 255 | |||||||||
| Net loss | $ | (56,824) | $ | (21,663) | |||||||
| Other comprehensive (loss) income: | |||||||||||
| Foreign currency translation adjustment | (5) | (22) | |||||||||
| Unrealized gain (loss) on marketable securities | — | 11 | |||||||||
| Total comprehensive loss | $ | (56,829) | $ | (21,674) | |||||||
| Net loss per share: | |||||||||||
| Basic and Diluted | $ | (10.50) | $ | (4.24) | |||||||
| Weighted-average common shares outstanding: | |||||||||||
| Basic and Diluted | 5,414,020 | 5,111,518 | |||||||||
Investor Contact
Ron Moldaver
ron.moldaver@cartesiantx.com
Media Contact
David Rosen
Argot Partners
cartesian@argotpartners.com
® THERAPEUTICS Pioneering mRNA Cell Therapy for Autoimmunity May 2024 C A R T E S I A N T H E R A P E U T I C S Exhibit 99.2
Forward-Looking Statements Disclosures For the purposes of this notice, the “presentation” that follows shall mean and include the slides that follow, the oral presentation of the slides by members of management of Cartesian Therapeutics, Inc. (the “Company”) or any person on their behalf, any question-and-answer session that follows such oral presentation, hard copies of this document and any materials distributed at, or in connection with, such oral presentation. Forward-looking Statements Any statements in this presentation about the future expectations, plans and prospects of the Company, including without limitation, statements regarding the Company’s expected cash resources and cash runway, the Company’s estimated cash on hand, conversion of the Company’s remaining Series A Non-Voting Convertible Preferred Stock, the Company’s in-house manufacturing capabilities, the potential of RNA Armory® to enable precision control and optimization of engineered cells for diverse cell therapies leveraging multiple modalities, the potential of Descartes-08, Descartes-15, Descartes-33 and the Company’s other product candidates to treat myasthenia gravis, systemic lupus erythematosus, or any other disease, the anticipated timing or the outcome of ongoing and planned clinical trials, studies and data readouts, the anticipated timing or the outcome of the FDA’s review of the Company’s regulatory filings, the Company’s ability to conduct its clinical trials and preclinical studies, the timing or making of any regulatory filings, the anticipated timing or outcome of selection of developmental product candidates, the ability of the Company to consummate any expected agreements and licenses and to realize the anticipated benefits thereof, the novelty of treatment paradigms that the Company is able to develop, the potential of any therapies developed by the Company to fulfill unmet medical needs, the Company’s ability to enter into and maintain its strategic partnerships, and enrollment in the Company’s clinical trials and other statements containing the words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “hypothesize,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including, but not limited to, the following: the uncertainties inherent in the initiation, completion and cost of clinical trials including proof of concept trials, including uncertain outcomes, the availability and timing of data from ongoing and future clinical trials and the results of such trials, whether preliminary results from a particular clinical trial will be predictive of the final results of that trial and whether results of early clinical trials will be indicative of the results of later clinical trials, the ability to predict results of studies performed on human beings based on results of studies performed on non-human subjects, the unproven approach of the Company’s RNA Armory® technology, potential delays in enrollment of patients, undesirable side effects of the Company’s product candidates, its reliance on third parties to conduct its clinical trials, the Company’s inability to maintain its existing or future collaborations, licenses or contractual relationships, its inability to protect its proprietary technology and intellectual property, potential delays in regulatory approvals, the availability of funding sufficient for its foreseeable and unforeseeable operating expenses and capital expenditure requirements, the Company’s recurring losses from operations and negative cash flows, substantial fluctuation in the price of the Company’s common stock, risks related to geopolitical conflicts and pandemics and other important factors discussed in the “Risk Factors” section of the Company’s most recent Annual Report on Form 10-K and Quarterly Reports on Form 10-Q, and in other filings that the Company makes with the Securities and Exchange Commission. In addition, any forward-looking statements included in this presentation represent the Company’s views only as of the date of its publication and should not be relied upon as representing its views as of any subsequent date. The Company specifically disclaims any intention to update any forward-looking statements included in this presentation, except as required by law. 2
3 Clinical-stage company pioneering mRNA cell therapies designed to expand the reach of cell therapy to autoimmunity • Pipeline of mRNA cell therapies designed to be dosed more reliably and safely in an outpatient setting without lymphodepletion • Descartes-08: Potential first-in-class mRNA CAR T-cell (CAR-T) demonstrated deep and durable clinical responses in Phase 2a study in patients with myasthenia gravis (MG) • Wholly-owned GMP manufacturing designed to enable rapid optimization of processes in iterative manner MULTIPLE ANTICIPATED NEAR-TERM CATALYSTS $104.8M as of March 31, 2024; expected to fund currently planned operations into 2H26 Expected to provide for continued clinical development of Descartes-08 in MG through Phase 3 and multiple additional clinical programs STRONG CASH RESOURCES • Phase 2b topline data in MG expected mid-2024 • Initiation of Phase 2 study in SLE expected in 1H 2024 • Initiation of studies in additional autoimmune indications expected in 2H 2024 DESCARTES-08 • Next-generation mRNA CAR-T candidate • IND cleared, with first-in-human Phase 1 planning activities underway DESCARTES-15 CAR, Chimeric antigen receptor SLE, Systemic Lupus Erythematosus
Experienced management team to lead the mRNA cell therapy company of the future Matthew Bartholomae General Counsel Metin Kurtoglu, MD, PhD CTO Milos Miljkovic, MD CMO Blaine Davis CFO Chris Jewell, PhD CSO Carsten Brunn, PhD President and CEO MANAGEMENT Emily English, PhD SVP, Head of Manufacturing Operations 4 BOARD MEMBERS Patrick Zenner Director Nishan De Silva, MD Director Timothy Springer, PhD Director Timothy Barabe Director Michael Singer, MD, PhD Director Carrie S. Cox Chairman Murat Kalayoglu, MD, PhD Director Jessica Keliher CPO
Cartesian’s mRNA approach is designed to expand the reach of potent cell therapy products to address potential autoimmune indications 5 Requires Lymphodepleting Chemotherapy Associated with high rates of toxicity, including cytokine release syndrome Conventional DNA Cell Therapy Permanent Cell Modification Associated with insertional mutagenesis leading to potential secondary malignancies Uncontrollable PK/PD Effector function of cell therapy engineered with DNA amplifies exponentially with cell replication Administered at Subtherapeutic Levels Cells proliferate rapidly beyond therapeutic window Requires Inpatient Administration High patient burden resulting in higher indirect costs Subtherapeutic Therapeutic window Toxicity C A R + C el ls Time mRNA Cell Therapy No Lymphodepleting Chemotherapy Required No requirement for cell proliferation no expected need for pre-treatment chemotherapy no Grade 3-4 cytopenias Transient Cell Modification Does not carry risk of genomic integration Controllable PK/PD mRNA does not replicate predictable half-life with more controllable PK/PD defined by the dose Delivered at Therapeutic Levels Expectation for cells to be administered at therapeutic, but sub-toxic doses Administered Outpatient Reduced patient burden and lower indirect cost Toxicity C A R + C el ls 6 Doses Therapeutic window Subtherapeutic Time ® THERAPEUTICS
Wholly-owned pipeline targets autoimmune disease SLE, Systemic Lupus Erythematosus * Phase 1 dose escalation study in myeloma underway mRNA MSC, Mesenchymal Stem Cells transfected with mRNA LN, Lymph node Asset Indications Discovery/Preclinical Phase 1 Phase 2 Pivotal Descartes-08 Autologous mRNA CAR-T Myasthenia Gravis SLE, other Autoimmune Diseases Descartes-15 Autologous mRNA CAR-T Autoimmune Diseases* Descartes-33 Allogeneic mRNA MSC Autoimmune Diseases In situ LN transfection Undisclosed 6
® THERAPEUTICS 7 Descartes-08 is believed to be the first mRNA CAR-T in clinical development for autoimmune disease Engineered by transfection of autologous CD8+ T cells with mRNA encoding anti-BCMA CAR Typical lot processed for infusion within ~3 weeks Positive Phase 2a data in myasthenia gravis underscores potential for deep and durable responses Granted U.S. FDA orphan designation for generalized myasthenia gravis
Descartes-08 is designed for dual action, precisely targeting two key BCMA+ cell populations involved in a spectrum of autoimmune diseases 8 Several autoimmune disease segments involve pathogenic contributions from both PCs/plasmablasts and pDCs, including rheumatology, nephrology, neurology, and others Selectively deleting PCs/plasmablasts and pDCs, if successful, may create a differentiated cell therapy platform PLASMA CELLS (PCs) AND PLASMABLASTS • PCs, plasmablasts and proliferating B cells targeted by Descartes-08 represent a tiny fraction of B cells • These cells are entirely responsible for secreting pathogenic autoantibodies • During autoimmunity, autoantibodies attack host tissue and drive inflammation PLASMACYTOID DENDRITIC CELLS (pDCs) • pDCs, which Descartes-08 is designed to target, are a rare subset of antigen-presenting cells • These cells secrete high levels of cytokines (i.e., type I interferons) that cause inflammation and tissue damage during many human autoimmune diseases • pDCs are increased in patients with autoimmunity (e.g., SLE) and interfere with optimal treatment • Descartes-08 is designed to target BCMA, a surface antigen expressed on plasma cells/plasmablasts and plasmacytoid dendritic cells BCMA: B cell maturation antigen; SLE: systemic lupus erythematosus
® THERAPEUTICS Initial indication for Descartes-08: Myasthenia gravis • Affects over 120,000 patients in US and EU • Characterized by debilitating weakness: limbs, respiratory, ocular, facial muscles • Standard of care includes chronic use of immunosuppressants, which are often toxic: • Progressive disease that is fatal in 1/3 of patients without immunosuppressants • Newer agents include complement inhibitors and anti-FcRn mAbs, which must be administered chronically to maintain responses • Pathogenesis is similar across many autoimmune diseases; involves attack on self by both T cells and B/plasma cells 9
Phase 2 study of Descartes-08 in MG (NCT04146051) All doses observed to be safe and well-tolerated 10 Patient eligibility • MG-ADL > 6 • MGFA Class II-IV • Stable medication dosing > 8 wks prior to infusion • 4-week washout for biologics • IVIg and plasma exchange not allowed after starting Descartes-08 Patients on immunosuppression or complement inhibitors expected to be able to continue their treatment while receiving Descartes-08 Cell manufacturing platform tolerates most standard immunosuppressive therapies Part 1 Identify safe dose (n = 3) Complete Part 2 Determine optimal dosing schedule (n = 11) Complete1 Part 3 Phase 2b comparing Descartes-08 to placebo (n = 30) Enrolling 1 Continues to enroll patients with MuSK MG and subjects who are otherwise not eligible for Part 3 MG-ADL, Myasthenia Gravis Activities of Daily Living scale MGFA, Myasthenia Gravis Foundation of America Six weekly infusions led to observed deep, durable responses Placebo-controlled trial for engineered adoptive cell therapy
® THERAPEUTICS Phase 1/2a study population comprises patients with significant disease • Baseline MG-ADL mean score of 10 • 79% were MGFA Class III-IV at screening • All patients presented with disease that was not controlled with standard of care therapies Volume 22, Issue 7, July 2023, Pages 578-590 11 Mean age, years (SD) 52 (18) Female 10 (71%) Male 4 (29%) Mean weight, kg (SD) 84 (21) Mean BMI, kg/m2 (SD) 31.6 (8.1) Race and ethnicity White, non-Hispanic 11 (79%) White, Hispanic 1 (7%) Asian 2 (14%) MGFA class at screening II 3 (21%) III 10 (71%) IV 1 (7%) Median age of disease onset, years (range) 40 (14-79) Median duration of disease, years (range) 14 (3-27) Myasthenia gravis antibody status Anti-AChR antibody 11 (79%) Anti-MuSK antibody 2 (14%) Seronegative (for AChR, MuSK, and LRP4 antibodies) 1 (7%) Mean baseline scores (SD) QMG 15.3 (4.1) MG-ADL 10.0 (3.2) MGC 21.9 (5.7) MG-QoL-15r 19.9 (5.8) Previous myasthenia gravis therapies (standard of care) Pyridostigmine 14 (100%) Prednisone 14 (100%) Other immunosuppressants 14 (100%) Eculizumab 2 (14%) Rituximab 2 (14%) Previous intravenous immunoglobin 12 (86%) Previous plasma exchange 8 (57%) Diagnosis of thymoma 0 Previous thymectomy 6 (43%) Previous myasthenia gravis crisis requiring intubation 4 (29%) Myasthenia gravis ongoing therapy Pyridostigmine 11 (79%) Prednisone 10 (71%) Azathioprine 1 (7%) Mycophenolate mofetil 1 (7%)
® THERAPEUTICS Descartes-08 was observed to be safe and well-tolerated in MG KEY OBSERVATIONS: • No dose-limiting toxicities • No cytokine release syndrome • No neurotoxicity • No pre-treatment chemotherapy and related cytopenias • Outpatient treatment Volume 22, Issue 7, July 2023, Pages 578-590 12 Grade* Part 1 (n=3) Part 2: all groups (n=11) Part 2: group 1 (n=3) Part 2: group 2 (n=7) Part 2: group 3 (n=1) Hand numbness 2 1 (33%) 0 0 0 0 Headache 1 1 (33%) 5 (45%) 1 (33%) 3 (43%) 1 (100%) Muscle soreness 1 1 (33%) 1 (9%) 0 1 (14%) 0 Nausea 1 1 (33%) 4 (36%) 2 (67%) 2 (29%) 0 Rash 3 0 1 (9%) 1 (33%) 0 0 Itchy throat 1 0 2 (18%) 0 1 (14%) 1 (100%) Vomiting 1 0 3 (27%) 2 (67%) 1 (14%) 0 Weakness 1 0 2 (18%) 2 (67%) 0 0 Line infiltration 1 0 1 (9%) 1 (33%) 0 0 Fever 1 0 4 (36%) 1 (33%) 3 (43%) 0 Shortness of breath1 1 0 2 (18%) 1 (33%) 1 (14%) 0 Chills 1 0 2 (18%) 1 (33%) 1 (14%) 0 Diarrhoea 1 0 1 (9%) 1 (33%) 1 (14%) 0 Gum inflammation 1 0 1 (9%) 0 1 (14%) 0 Teeth sensitivity 1 0 1 (9%) 0 1 (14%) 0 Night sweats 1 0 1 (9%) 0 1 (14%) 0 Restless leg 1 0 1 (9%) 0 1 (14%) 0 Light-headedness 1 0 1 (9%) 0 1 (14%) 0 *There were no adverse events of grade 3 or higher reported in part 1, and no grade 2 or grade 4 events reported in part 2, where grade 1 is mild, grade 2 is moderate, grade 3 is severe, and grade 4 is life- threatening. 1Not associated with hypoxia
® THERAPEUTICS Descartes-08 observed to induce deep and durable clinical improvement in MG • Notable magnitude and duration of response across all 4 standard MG severity scales • Responses appear to deepen after completing treatment at Week 6 • Positive twelve-month follow-up data from Phase 2a study reinforce prior findings published in Lancet Neurology 13 Manuscript submitted for peer review; pre-print available at medRxiv.org Efficacy dataset includes all MG patients completing the 6-dose once-weekly regimen (n=7). Data are mean score improvement (point) and standard error (light blue shading). Note that QOL scale does not have an agreed-upon threshold for clinically meaningful disease improvement; MG-ADL, MGC and QMG scales are validated, quantitated, standardized instruments of disease severity and have been acceptable endpoints for registration studies.
® THERAPEUTICS 14 Descartes-08: Durable depletion of autoantibodies consistent with observed clinical responses and MoA • All three participants with detectable AChR antibody levels at baseline experienced autoantibody reductions by Month 6 • Reductions deepened further by Month 9, and were maintained at Month 12 Manuscript submitted for peer review; pre-print available at medRxiv.org Anti-acetylcholine receptor, AChR MoA, Mechanism of action
® THERAPEUTICS 15 Descartes-08 retreatment led to a rapid decrease in MG-specific clinical scores • Retreated patients experienced rapid improvement in clinical scores and minimal symptom expression Manuscript submitted for peer review; pre-print available at medRxiv.org Pa tie nt 1 Pa tie nt 2
Informed Consent/Screening (Days -61 to -12) Screening (Days -60 to -11) Leukapheresis & Cell Processing (Days -59 to -10) Descartes-08 (Day 1, 8, 15, 22, 29, 36) Placebo (Day 1, 8, 15, 22, 29, 36) Follow up visits Day 57 (± 7 days) Day 85* (± 7 days) Day 113 (± 7 days) Month 6 (± 2 weeks) Month 9 (± 2 weeks) Month 12 (± 2 weeks) Descartes-08 (Crossover Day 1, 8, 15, 22, 29, 36) Follow up visits Crossover Day 57 (± 7 days) Crossover Day 85* (± 7 days) Crossover Day 113 (± 7 days) Crossover Month 6 (± 2 weeks) Crossover Month 9 (± 2 weeks) Crossover Month 12 (± 2 weeks) Phase 2b randomized, placebo-controlled, double-masked study of Descartes-08 in MG Enrollment underway, with top-line results expected in mid-2024 Plan to treat ~30 patients PRIMARY ENDPOINT • Proportion of MG Composite responders (≥5-point reduction) at Day 85 SECONDARY OBJECTIVES • Safety and tolerability • Quantify clinical effect of Descartes-08 over 1 year • QMG, MG QoL 15R, MG ADL, and MG PIS (change from baseline to Day 85) • Compare effect of Descartes-08 versus placebo on MG scales (change from baseline to Day 85) in patients who cross over from placebo to Descartes-08 16 Randomization MG QMG, Quantitative MG Scores MG QOL15R, MG Quality of Life 15-revised MG ADL, MG Activities of Daily Living MG PIS, MG Post-intervention Status
Exploring potential of Descartes-08 in Systemic Lupus Erythematosus (SLE) 17 • Open-label study in up to 30 adults with moderate to severe multi-refractory SLE and no CNS involvement • Designed to assess safety, tolerability, and manufacturing feasibility of Descartes-08 in patients with SLE • Secondary objectives include standard measures of clinical activity in SLE: • Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) • Physician Global Assessment (PGA) • Systemic Lupus Erythematosus Responder Index (SRI) • British Isles Lupus Assessment Group (BILAG)–based Composite Lupus Assessment (BICLA) Screening (Days -60 to -15) Leukapheresis & Cell Processing (Days -59 to -14) 2 - 3 Weeks Descartes-08 (Day 1, 8, 15, 22, 29, 36) Safety/Response Assessment (Day 50) Follow up visits (Months 3, 6, 9, 12) IND CLEARED PHASE 2 STUDY ON TRACK FOR 1H 2024
Exploring additional applications for Descartes-08 in autoantibody- associated autoimmune diseases (AAAD) 18 61-year-old man with DPPX antibody-positive AIR, colitis, encephalitis refractory to prednisone, rituximab, bortezomib, IVIg; positive for 5/5 disease-associated autoantibodies pre-treatment Post-treatment: experienced a clinically-significant, 2-line improvement in visual acuity; 3 of 5 autoantibodies became undetectable Potential significant Descartes-08-associated improvement observed in a patient with autoimmune retinitis (AIR) Test Pre-treatment Month 2 Month 4 Month 6 Visual acuity 20/60 20/40 20/40 20/40 Carbonic anhydrase II Ab + - - NP* Tubulin Ab + - - NP* PKM2 Ab + - - NP* Aldolase Ab + + + NP* Enolase Ab + + + NP* *NP – not performed • Clinical data suggest that Descartes-08 could lead to clinical benefit along with disappearance of disease-associated autoantibodies, suggesting potential in additional autoimmune indications DPPX, Dipeptidyl-peptidase–like protein 6 IVIg, Intravenous immunoglobulin
RNA Armory® example: Descartes-15, a next generation anti-BCMA mRNA CAR-T with >10x potency observed in preclinical studies Potent killing (single target exposure) Persistent killing (multiple exposures) (1:2) (1:8) (1:32) 0 50 100 % S pe ci fic K ill in g DC-15 DC-08 Vehicle EP escartes-08 escartes-15 Control (1:2) (1:8) (1:32) 0 50 100 % S pe ci fic K ill in g DC-15 DC-08 Vehicle EP escartes-08 escartes-15 Control Descartes-15 is an anti-BCMA mRNA CAR-T with potential disruptive features: • Engineered for maximum potency and CAR stability, even in the presence of target-driven suppression of CAR • Clinical strategy expected to leverage safety and clinical activity data from Descartes-08 Day 0 Day 1 Day 2 Day 5 Day 7 Day 9 0 1000 2000 3000 M FI DC-15 DC-08 Vehicle EP escartes-08 escartes-15 Control Superior CAR expression Contro l Des ca rte s-1 5 0 2×108 4×108 6×108 8×108 Day 21 To ta l F lu x (p /s ) Control Descartes-15 Contro l Des ca rte s-1 5 0 1×107 2×107 3×107 Day 11 To ta l F lu x (p /s ) Day 21Day 11Efficient killing of BCMA+ target cells1 Day 11 1 MM1-S disseminated myeloma model in NSG mice infused with either control T-cells or Descartes-15 19
® THERAPEUTICS 20 In-house manufacturing enhances control of product quality, production schedules and costs cGMP Cell Manufacturing ISO14644 certified aseptic facility with dedicated QMS cGMP mRNA Synthesis Clinical grade mRNA production Quality Control Internal assay validation and lot release MSC Cell Banking Part 1271, FDA- reviewed huMSC collection & banking Process Development Processes optimized through >200 cGMP runs
Wholly-owned, in-house manufacturing: 27,000 sq ft state-of-the-art cGMP facility Ownership of quality control and production timelines Flexibility to quickly adapt to changes in processes or needs Cost efficiency Clinical and commercial manufacturing scale capabilities support maturing pipeline and future growth cGMP, current good manufacturing practice Facility located in Frederick, MD
Platform offers potential development opportunities via three modalities: autologous, allogeneic and in situ 22 Autologous mRNA CAR-T • Descartes-08 • Descartes-15: next generation anti- BCMA mRNA CAR-T with >10x potency observed in clinical studies Allogeneic mRNA MSC • Descartes-33 rLN: In situ lymph node transfection • Undisclosed program
Maturing pipeline offers potential for multiple catalysts 23 Descartes-08 in MG Descartes-08 in SLE Descartes-08 Additional Indications Descartes-15 Expect to report Phase 2b data mid-2024 Plan to initiate Phase 2 in 1H 2024 Plan to initiate basket studies in additional autoimmune indications in 2H 2024 IND cleared, with first-in-human Phase 1 planning activities underway M id 2024 1H 2024 2H 2024 2024 Funding expected to support development of Descartes-08 through Phase 3 and advance additional programs
® THERAPEUTICS Strong Financial Position Expected to Support Pipeline Through Key Milestones <60 EMPLOYEES 2H 2026 17.8M *Shares include approximately 166.3 thousand shares of Series A Non-Voting Convertible Preferred Stock that remain subject to beneficial ownership limitations that are convertible into approximately 5.5 million shares of common stock. **Fully diluted shares include diluted shares as described above, as well as outstanding options, RSUs and warrants. $104.8M Cash as of 3/31/24 Anticipated cash runway into Based in Gaithersburg, MD 23.3M Fully diluted shares outstanding** Basic shares outstanding Basic shares outstanding upon full conversion of outstanding Series A Preferred* 26.6M 24
® THERAPEUTICS P I O N E E R I N G m R N A C E L L T H E R A P I E S Pipeline designed to expand the reach of cell therapy to autoimmunity M A T U R I N G P I P E L I N E W I T H E X P E C T E D N E A R - T E R M C A T A L Y S T S Validated lead program, Descartes-08, with Phase 2b data expected mid-year C A S H R E S O U R C E S E X P E C T E D T O F U N D O P E R A T I O N S I N T O 2 H 2 0 2 6 Expected to support Descartes-08 through Phase 3 and advance additional programs E X P E R I E N C E D L E A D E R S H I P T E A M ® THERAPEUTICS Focused on disciplined investment and creating value for stockholders and patients
® THERAPEUTICS Pioneering mRNA Cell Therapy for Autoimmunity C A R T E S I A N T H E R A P E U T I C S
® THERAPEUTICS Appendix
Differentially expressed B-cell antigens require distinct CAR-T strategies • CD19+ and CD20+ cells represent the vast majority of B cells and are ubiquitously distributed • CD19+ and CD20+ are often expressed on the same B cells • The exceptions are plasma cells, in which neither antigen is expressed, and plasmablasts, in which CD19+ is expressed, directly responsible for pathogenic autoantibodies • Plasma cells are rare and tissue-restricted 28 Sender et al., PNAS 2023 BCMA is a differentiated target with potential for precision CAR-T in patients with autoimmunity CD19+ CD20+ BCMA+
® THERAPEUTICS Clinical analyses of antigen-depletion therapies show BCMA-targeting with CAR-T may enable precision reset of autoantibody- producing PCs 29Bodansky et al., doi: 10.1101/2023.12.19.23300188 Rituximab (CD20+ cell depletion) Anti-CD19 CAR-T (CD19+ cell depletion) Anti-BCMA CAR-T (BCMA+ cell depletion) Minimal change in autoreactivity Minimal change in autoreactivity Nearly full reset of autoreactivity
Cartesian differentiation: All approved CAR T therapies and other trials in the autoimmune space face fundamental hurdles created by integrating vectors 30 Conventional CAR-T (integrating viral vectors) targeting CD19 • Creates significant burden for patients in three areas • hospital admission • lymphodepletion/chemotherapy • cytokine release syndrome (CRS) risk • Patients with autoimmunity typically have much lower tolerance for these hurdles relative to cancer patients mRNA CAR T (no integration) targeting BCMA • mRNA enables transient expression no need for significant T cell proliferation • Eliminates lymphodepletion and enables outpatient administration without CRS