Advancing clinical development of MT-6402, MT-8421, and MT-0169, and preclinical activities related to
Company Highlights
- Clinical data for each program has demonstrated novel mechanisms of action, unique pharmacodynamic (“PD”) effects, and single agent activity in heavily relapsed / refractory patients across immuno-oncology, hematologic, and solid tumor indications.
- To date, no instances of capillary leak syndrome or other manifestations of innate immunity have been observed with any next-generation ETB.
- MT-6402 Phase I dose escalation continues at 100 mcg/kg. As of
May 2023 , patients with r/r tumors expressing PD-L1 have been treated across six dose escalation cohorts: 16 mcg/kg, 24 mcg/kg, 32 mcg/kg, 42 mcg/kg, 63 mcg/kg and 83 mcg/kg with clearance of immune cells in a PD-L1 targeted fashion and increases in cytokines associated with T-cell activation. - A MT-6402 patient in cohort 5 (63 mcg/kg) with metastatic squamous cell nasopharynx carcinoma with disease progression after radiation therapy, chemotherapy, and pembrolizumab had a Partial Response (“PR”) (RECIST) with a 63% reduction in the index lesion after cycle 2. The PR was confirmed after cycle 4 with a 66% reduction, and the patient remains on treatment and in a response in cycle 7. This patient’s tumor had 2% PD-L1 expression and the patient is not HLA-A*02, suggesting the response is due to T-cell activation through the clearance of PD-L1+ immune cells. The patient showed a >250% increase in CD8/CD4 T-cell ratios.
- An IND for MT-8421 was accepted on
March 8, 2023 , with the first-in-human phase I study anticipated to begin by mid-year2023. MT -8421 targets CTLA-4-expressing Tregs in the TME for elimination without affecting Tregs in the periphery. - In
April 2023 , the FDA placed the Phase I study for MT-0169 on a partial clinical hold based on previously disclosed cardiac AEs noted in two patients dosed at 50 mcg/kg that prompted the dose reduction to 5 mcg/kg last year. Current study participants may continue treatment. MTEM has submitted its response to the partial hold to the FDA and anticipates feedback from the agency by the end of May. No cardiotoxicity was seen in patients treated at 5 mcg/kg or 10 mcg/kg; one patient treated at 5 mcg/kg remains in a stringent Complete Response at cycle 9. - MTEM retains
Stifel, Nicolaus & Company, Incorporated to assist in exploring strategic and financing alternatives.
MT-6402 (PD-L1-targeting ETB with Antigen Seeding Technology)
- MT-6402 was designed to activate T-cells through direct cell-kill of immunosuppressive PD-L1+ immune cells.
- In addition, MT-6402 can deliver and induce the presentation of an MHC class I CMV antigen on tumor cells (antigen seeding mechanism of action) for pre-existing CD8 T-cell recognition and destruction in HLA-A*02/CMV+ patients with high PD-L1 expression on their tumors.
- MT-6402 continues to demonstrate PD effects and monotherapy activity in heavily pre-treated checkpoint therapy experienced patients.
- Dose escalation continues in the MT-6402 phase I study in relapsed/refractory solid tumor patients with PD-L1-expressing tumors and/or PD-L1 expressing immune cells in the TME. Highlights from the on-going Phase I study:
- As of
May 2023 , patients have been treated across six dose escalation cohorts of 16 mcg/kg, 24 mcg/kg, 32 mcg/kg, 42 mcg/kg, 63 mcg/kg and 83 mcg/kg in the MT-6402 study of patients with relapsed/refractory tumors that express PD-L1. Dose escalation continues with patients being recruited at 100 mcg/kg. - We continue to observe pharmacodynamic (“PD”) effects including the depletion of PD-L1+ monocytes, MDSCs, PD-L1+ dendritic cells, as well as T cell activation.
- One patient in cohort 5 (63 mcg/kg) with metastatic squamous cell nasopharynx carcinoma with disease progression after radiation therapy, chemotherapy, and pembrolizumab had a Partial Response (“PR”) (RECIST) with a 63% reduction in the index lesion after cycle 2. The patient remains in a confirmed response at cycle 7.
- Treatment-related AEs including immune-related AEs have been largely restricted to grade 1-2.
- As of
- Two Phase I dose expansion cohorts are planned for 2023 including for patients with high PD-L1 tumor expression and for patients with low PD-L1 tumor expression.
MT-8421 (CTLA-4 ETB)
- MT-8421 was designed to target CTLA-4 in a wholly distinct manner from the current monoclonal antibody approaches. MT-8421 was designed to preferentially destroy high CTLA-4-expressing Tregs in the TME relative to peripheral Tregs which are lower CTLA-4 expressing, through an enzymatic ribosomal direct cell-kill mechanism independent of the TME.
- MT-8421 was also designed to avoid CTLA-4 blockade in the periphery, the major mechanism of antibody-mediated autoimmune toxicity.
- The IND for MT-8421 was filed in
February 2023 and accepted inMarch 2023 . - The first-in-human Phase 1 study is expected to start by mid-year 2023.
- MT-8421 and MT-6402 represent a unique approach to immuno-oncology based on dismantling the TME through direct cell-kill of tumor and immune cells.
MT-0169 (CD38 ETB)
- MT-0169 was designed to destroy CD38+ tumor cells through internalization of CD38 and cell destruction via a novel mechanism of action (enzymatic ribosomal destruction and immunogenic cell death).
- In
April 2023 , the FDA placed the Phase I study for MT-0169 on a partial clinical hold based on previously disclosed cardiac AEs noted in two patients dosed at 50 mcg/kg that prompted the dose reduction to 5 mcg/kg last year. MTEM has submitted its response to the partial hold to the FDA and anticipates feedback from the agency by the end of May. - A stringent Complete Response was seen in a patient with extramedullary IgA myeloma treated at 5 mcg/kg. The patient had a marked reduction in IgA serum protein, conversion from immunofixation positive to negative, and resolution of uptake on bone scan of skeletal lesions. The patient’s disease was quad-agent refractory including CD38-targeting, proteosome inhibitor, IMiD, and a BCMA bispecific antibody. The patient continues on study in Cycle 9.
Research and Collaboration
- MTEM continues to expand and develop its unique approach to oncology targets in its collaboration with
Bristol Myers Squibb .
Key Milestones for 2023
- Accelerating enrollment across clinical programs
- Initiation of first-in-human Phase I study for MT-8421 mid-year
- Advancement of
Bristol Myers Squibb research collaboration across multiple targets - MTEM expects to provide periodic updates on MT-6402, MT-8421, and MT-0169 throughout 2023.
Conferences
- MTEM presented an abstract, “Engineered Toxin Bodies (ETBs): Clinical stage immunotoxins with a safer and differentiated profile”,
Monday, April 17, 2023 ,1:30pm –5pm ET (Section 13, Poster Board No 29, No. 2661)), at theAmerican Association for Cancer Research (“AACR”) Annual Meeting which took place at theOrange County Convention Center inOrlando, FL fromApril 14 – 19, 2023. The abstract is visible in the presentations section of the corporate website. - MTEM will present a poster on updated clinical data on MT-6402 (ETB targeting PD-L1),
June 3, 2023 , at the 2023American Society for Clinical Oncology (ASCO) Annual Meeting taking place atMcCormick Place inChicago, Illinois and virtually fromJune 2 – 6, 2023. The poster will be visible in the presentations section of the corporate website. One-on-one meetings may be scheduled by directly contactingMolecular Templates . - MTEM will participate at the
BIO International conference taking place at theBoston Convention and Exhibition Center inBoston, MA fromJune 5 – 8, 2023. One-on-one meetings may be scheduled by directly contactingMolecular Templates . - MTEM will present a virtual fireside chat
Wednesday, June 7, 2023 , at theJefferies Healthcare Conference taking place at theMarriott Marquis inNew York, NY fromJune 7 – 9, 2023. The presentation will be accessible via the corporate website. One-on-one meetings may be scheduled by directly contactingMolecular Templates .
Financial Results
The net income attributable to common shareholders for the first quarter of 2023 was
Revenues for the first quarter of 2023 were
Total research and development expenses for the first quarter of 2023 were
On
As of
Process to Explore Strategic Alternatives
MTEM has an ongoing process to explore a range of strategic and financing alternatives to maximize shareholder value. In addition to continuing to explore any available financing alternatives to maintain continued compliance with the covenants and restrictions under the K2 Loan and Security Agreement as described above and to lengthen its cash runway, MTEM’s process will also focus on identifying and evaluating any other strategic alternatives, including potentially the sale of all, or part, of the Company, or a merger. MTEM has retained the investment bank
About
Forward-Looking Statements
This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the “Act”). Molecular Templates disclaims any intent or obligation to update these forward-looking statements and claims the protection of the Act’s Safe Harbor for forward-looking statements. All statements, other than statements of historical facts, included in this press release regarding strategy, future operations, future financial position, future revenue, projected expenses, prospects, plans and objectives of management are forward-looking statements. In addition, when or if used in this press release, the words “may,” “could,” “should,” “anticipate,” “believe,” “estimate,” “expect,” “intend,” “plan,” “predict” and similar expressions and their variants, as they relate to Molecular Templates may identify forward-looking statements. Examples of such statements include, but are not limited to, statements regarding Molecular Templates’ continued compliance with the financial covenant and solvency requirements in the K2 Loan and Security Agreement; Molecular Templates’ cash runway and continued operations; and the future possibility of a strategic transaction or financing alternative to maintain continued compliance with the covenants and restrictions in the K2 Loan and Security Agreement; the safety or potential efficacy of Molecular Templates’ drug or biologic candidates; Molecular Templates’ belief that its proprietary biologic drug platform technology, or ETBs, provides for a differentiated mechanism of action for cancer; and the prospects for continued clinical development and regulatory approval. Forward-looking statements are not guarantees of future performance and involve risks and uncertainties. Actual events or results may differ materially from those discussed in the forward-looking statements as a result of various factors including, but not limited to the following: whether
Contacts:
Dr.
Head of Investor Relations
grace.kim@mtem.com
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS
(in thousands, except share and per share data)
(unaudited)
Three Months Ended | |||||||
2023 | 2022 | ||||||
Research and development revenue | $ | 33,627 | $ | 8,486 | |||
Grant revenue | 3,002 | — | |||||
Total revenue | 36,629 | 8,486 | |||||
Operating expenses: | |||||||
Research and development | 19,042 | 21,497 | |||||
General and administrative | 5,802 | 7,620 | |||||
Total operating expenses | 24,844 | 29,117 | |||||
Income/(loss) from operations | 11,785 | (20,631 | ) | ||||
Interest and other income, net | 455 | 70 | |||||
Interest and other expense, net | (1,395 | ) | (1,050 | ) | |||
Net income/(loss) | $ | 10,845 | $ | (21,611 | ) | ||
Net income/(loss) per share attributable to common shareholders: | |||||||
Basic and diluted | $ | 0.19 | $ | (0.38 | ) | ||
Weighted average number of shares used in net income/(loss) per share calculations: | |||||||
Basic and diluted | 56,351,647 | 56,305,049 |
CONDENSED CONSOLIDATED BALANCE SHEETS
(in thousands, except share and per share data)
2023 (unaudited) | 2022 | |||||||
ASSETS | ||||||||
Current assets: | ||||||||
Cash and cash equivalents | $ | 38,782 | $ | 32,190 | ||||
Marketable securities, current | 2,889 | 28,859 | ||||||
Prepaid expenses | 2,009 | 3,459 | ||||||
Grants revenue receivable | 2,838 | — | ||||||
Other current assets | 5,106 | 3,790 | ||||||
Total current assets | 51,624 | 68,298 | ||||||
Operating lease right-of-use assets | 10,652 | 11,132 | ||||||
Property and equipment, net | 12,814 | 14,632 | ||||||
Other assets | 3,415 | 3,486 | ||||||
Total assets | $ | 78,505 | $ | 97,548 | ||||
LIABILITIES AND STOCKHOLDERS’ EQUITY | ||||||||
Current liabilities: | ||||||||
Accounts payable | $ | 2,718 | $ | 504 | ||||
Accrued liabilities | 5,542 | 8,823 | ||||||
Deferred revenue, current | 19,354 | 45,573 | ||||||
Other current liabilities | 2,286 | 2,182 | ||||||
Total current liabilities | 29,900 | 57,082 | ||||||
Deferred revenue, long-term | 1,156 | 5,904 | ||||||
Long-term debt, net of current portion | 36,402 | 36,168 | ||||||
Operating lease liabilities | 11,635 | 12,231 | ||||||
Other liabilities | 1,322 | 1,295 | ||||||
Total liabilities | 80,415 | 112,680 | ||||||
Commitments and contingencies | ||||||||
Stockholders’ deficit | ||||||||
Preferred stock, | ||||||||
Authorized: 2,000,000 shares at | — | — | ||||||
Common stock, | ||||||||
Authorized: 150,000,000 shares at | 56 | 56 | ||||||
Additional paid-in capital | 431,956 | 429,646 | ||||||
Accumulated other comprehensive income/(loss) | 1 | (66 | ) | |||||
Accumulated deficit | (433,923 | ) | (444,768 | ) | ||||
Total stockholders’ deficit | (1,910 | ) | (15,132 | ) | ||||
Total liabilities and stockholders’ deficit | $ | 78,505 | $ | 97,548 |
Source:
2023 GlobeNewswire, Inc., source