MATINAS BIOPHARMA HOLDINGS, INC. Clear registration pathway and FDA agreement on the ORALTO Phase 3 trial for MAT2203 represent critical steps forward and supports partnership discussions
Continued success of Compassionate/Expanded Use Access Program demonstrates potential of MAT2203 in treating multiple severe invasive fungal infections, including invasive aspergillosis
Successful in vivo LNC platform studies demonstrating (a) the oral delivery of small oligonucleotides with biological activity and (b) the dramatically improved safety of LNC-docetaxel over IV-docetaxel, with similar efficacy, supports the future use of the LNC platform in inflammation and oncology
Conference call begins at
“A clear regulatory approval pathway for oral MAT2203 is a critical step toward future commercialization in its initial indication of the treatment of invasive aspergillosis in patients with limited treatment options,” said
“We have also advanced the application of our LNC platform into exciting areas, including oncology and inflammation. In the oncology space, our in vivo data demonstrate that treatment with oral LNC-docetaxel at dosages substantially higher than those proven effective in targeting melanoma tumors resulted in tumor size reductions comparable to IV-docetaxel and was associated with none of the toxicity (body weight loss) observed with conventional IV-docetaxel. In the field of inflammation, we have demonstrated the successful oral delivery of biologically active – and potentially therapeutic – small oligonucleotides in several inflammatory disease models.
“Overall, we are pleased with all of the progress made by our team throughout 2023 and so far in 2024, and our focus remains on executing our strategic plan to make the LNC platform the preferred next-generation orally available intracellular drug delivery technology, facilitating an internal and external pipeline of drug candidates.”
Key Program Updates
MAT2203 (Oral Amphotericin B) Program
Phase 3 ORALTO Registration Trial
- Matinas reached alignment with the FDA on the design of a single Phase 3 registration trial of oral MAT2203 in patients with invasive aspergillosis
who have limited treatment options. This is a serious and life-threatening invasive fungal infection that occurs primarily in severely immunocompromised patients, including those with hematological malignancies and in transplant recipients. In 2022, theWorld Health Organization released its Fungal Priority Pathogen List that designated the most common invasive aspergillosis, Aspergillus fumigatus, to be in the Critical Priority group, which is designated as the highest perceived public health threat. Aspergillus fumigatus is also included in the FDA qualified designation list of pathogens that pose a serious and life-threatening risk. - The Phase 3 randomized, multicenter, open-label, adjudicator-blinded ORALTO trial will evaluate the efficacy and safety of MAT2203 as an oral step-down treatment following two days of treatment with AmBisome® (liposomal IV-amphotericin B) compared with the standard of care in patients with invasive aspergillosis
who have limited treatment options. The primary efficacy endpoint in this non-inferiority study is all-cause mortality at study day 42. Key secondary objectives include demonstration of superiority for treatment-related toxicities leading to changes in treatment, long-term survival benefit of MAT2203 using all-cause mortality at study day 84 and the impact of MAT2203 on healthcare resource utilization and quality of life. - The Phase 3 ORALTO trial is expected to include approximately 65 investigator sites in the
U.S. ,Europe ,South America , theMiddle East andAsia Pacific . Enrollment is expected to include approximately 216 adults with recently diagnosed probable or proven invasive aspergillosiswho are being treated with AmBisome due to their inability to receive an IV mold-active azole and with limited alternative treatment options. Following up to two days of treatment with AmBisome, eligible participants will be randomized 2:1 to receive either oral MAT2203 or continued AmBisome treatment followed by standard of care. All study participants will receive up to 12 weeks of treatment starting from the first day of treatment with AmBisome. All study participants are expected to be hospitalized during the initial AmBisome treatment period. After step-down to oral MAT2203, study participants may be discharged to continue treatment on an outpatient basis, as clinically appropriate. An independent Data Review Committee, which will be blinded to treatment, will adjudicate primary and secondary endpoints, including clinical, radiological, and mycological responses. - Once approximately 75% of participants are enrolled, an independent Data Safety Monitoring Board will review the pooled all-cause mortality rate in a blinded fashion to ensure sample size assumptions are reasonable and the study is adequately powered. Should the pooled event differ substantially from expected levels, a sample size adjustment can be made to the trial.
- The Company is engaged in active dialogues with potential partners and is seeking to finalize a partnership as soon as possible in order to commence the Phase 3 ORALTO trial.
MAT2203 Compassionate/Expanded Use Access Program
- A total of 19 patients with serious/life-threatening invasive fungal infections have been enrolled in the program to date, with others being evaluated. The infections treated include a variety of micro-organisms (including Aspergillus, Mucorales species, Candidiasis, Fusarium and suspected Coccidioides) at multiple sites of infection including brain, bladder/colon, bone, lung, sinus, and skin. The majority of enrolled patients are post-transplant or are undergoing treatment for underlying malignancies.
- Patients have been enrolled in the Program at prestigious institutions including the
University of Michigan ,Johns Hopkins , Nationwide Children’s Hospital, City of Hope,Vanderbilt University Medical Center , theNational Institutes of Health , Children’s Hospital ofPhiladelphia ,Memorial Sloan Kettering Cancer Center and theUniversity of California ,San Diego School of Medicine . - Most patients were receiving AmBisome prior to enrollment but developed treatment-limiting nephrotoxicity, and most also required treatment for azole-resistant organisms or had failed azole therapy and had no other treatment options. All patients
who transitioned to MAT2203 after developing renal toxicity following treatment with AmBisome experienced a reversal of renal impairment with a return to baseline renal function and no subsequent renal issues. In addition, most patients to date were able to be discharged from the hospital setting and effectively treated at home, supporting the potential significant pharmacoeconomic impact of MAT2203. - Eight patients
who completed the desired course of treatment with oral MAT2203 had complete clinical resolution of their infection and patients with ongoing treatment continue to experience significant clinical improvement.
LNC Platform Updates
Internal Oral LNC Oncology Program
- Conventional docetaxel, a well-known chemotherapeutic agent used in the management of multiple metastatic and unresectable tumors, is only administered intravenously, and is associated with significant side effects and toxicities.
- LNC’s crystalline structure encapsulates and protects the body from the docetaxel cargo and selectively delivers drug to tumor cells. This markedly reduces the amount of free drug circulated systemically, avoiding one of the primary drivers of toxicity.
- LNC-docetaxel is an effective targeting vehicle and an efficient delivery platform for oncology applications due to its unique phospholipid composition that allows for targeting and delivering docetaxel to tumor cells that express phosphatidylserine on their surface.
- In vivo study data reported in
November 2023 demonstrated that oral LNC-docetaxel effectively targeted melanoma tumors and was able to reduce tumor sizes to a degree comparable to that of IV-docetaxel with no apparent toxicity. - Additional in vivo study data reported in
March 2024 corroborated the lack of toxicity in a more comprehensive safety study with a longer treatment duration and higher doses of oral LNC-docetaxel. Healthy mice administered oral LNC-docetaxel at doses more than 8x greater than IV-docetaxel showed no weight loss, versus an average 20% peak weight loss in mice treated with IV-docetaxel. Mice treated with oral LNC-docetaxel maintained their body weight, which was statistically no different than the weight of control mice treated with oral saline.
Internal Oral LNC Small Oligonucleotide Inflammation Program
- In vivo studies documented the successful oral delivery and biological activity of two different LNC-formulated small oligonucleotides targeting inflammatory cytokines IL-17A and TNFα with reductions in tissue cytokine mRNA in both colitis and psoriasis, along with significant reductions in serum TNFα levels in colitis.
- The LNC-formulated small oligonucleotides evaluated in these studies interfered with cytokine synthesis rather than simply targeting the cytokine itself, which creates additional opportunities for potential future applications of LNC-delivered therapeutics.
Corporate Development
- The Company received notification from the
NYSE American LLC that it has regained compliance with theNYSE American LLC continued listing standards by resolving the continued listing deficiency with respect to the low selling price of its common stock as described in Section 1003(f)(v) of the NYSE American Company Guide.
2023 Financial Results
Revenue for 2023 was
Total costs and expenses for 2023 were
The net loss for 2023 was
Cash, cash equivalents and marketable securities as of
Conference Call and Webcast
Matinas will host a conference call and webcast today beginning at
About
Matinas’ lead LNC-based therapy is MAT2203, an oral formulation of the broad-spectrum antifungal drug amphotericin B, which although highly potent, can be associated with significant toxicity. Matinas’ LNC platform provides oral delivery of amphotericin B without the significant nephrotoxicity otherwise associated with IV-delivered formulations. Combining comparable fungicidal activity with targeted delivery results in a lower risk of toxicity and potentially creates the ideal antifungal agent for the treatment of invasive fungal infections. MAT2203 was successfully evaluated in the completed Phase 2 EnACT study in HIV patients suffering from cryptococcal meningitis, meeting its primary endpoint and achieving robust survival. MAT2203 will be further evaluated in a single Phase 3 registration trial (the “ORALTO” trial) as an oral step-down monotherapy following treatment with AmBisome® (liposomal amphotericin B) compared with the standard of care in patients with invasive aspergillosis
In addition to MAT2203, preclinical and clinical data have demonstrated that this novel technology can potentially provide solutions to many challenges of achieving safe and effective intracellular delivery of both small molecules and larger, more complex molecular cargos including small oligonucleotides such as ASOs and siRNA. The combination of its unique mechanism of action and flexibility with routes of administration (including oral) positions Matinas’ LNC technology to potentially become a preferred next-generation orally available intracellular drug delivery platform. For more information, please visit www.matinasbiopharma.com.
Forward-looking Statements
This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including those relating to our business activities, our strategy and plans, the potential of our LNC platform technology, and the future development of its product candidates, including MAT2203, the Company’s ability to identify and pursue development, licensing and partnership opportunities for its products, including MAT2203, or platform delivery technologies on favorable terms, if at all, and the ability to obtain required regulatory approval and other statements that are predictive in nature, that depend upon or refer to future events or conditions. All statements other than statements of historical fact are statements that could be forward-looking statements. Forward-looking statements include words such as "expects," "anticipates," "intends," "plans," "could," "believes," "estimates" and similar expressions. These statements involve known and unknown risks, uncertainties and other factors which may cause actual results to be materially different from any future results expressed or implied by the forward-looking statements. Forward-looking statements are subject to a number of risks and uncertainties, including, but not limited to, our ability to continue as a going concern, our ability to obtain additional capital to meet our liquidity needs on acceptable terms, or at all, including the additional capital which will be necessary to complete the clinical trials of our product candidates; our ability to successfully complete research and further development and commercialization of our product candidates; the uncertainties inherent in clinical testing; the timing, cost and uncertainty of obtaining regulatory approvals; our ability to protect the Company’s intellectual property; the loss of any executive officers or key personnel or consultants; competition; changes in the regulatory landscape or the imposition of regulations that affect the Company’s products; and the other factors listed under "Risk Factors" in our filings with the
Investor Contact:
LHA Investor Relations
Jcain@lhai.com
310-691-7100
[Financial Tables to Follow]
Consolidated Balance Sheets (in thousands, except for share data) | ||||||||
| 2023 | 2022 | |||||||
| ASSETS: | ||||||||
| Current assets: | ||||||||
| Cash and cash equivalents | $ | 4,787 | $ | 6,830 | ||||
| Marketable debt securities | 8,969 | 21,933 | ||||||
| Restricted cash – security deposit | 50 | 50 | ||||||
| Prepaid expenses and other current assets | 1,737 | 5,719 | ||||||
| Total current assets | 15,543 | 34,532 | ||||||
| Non-current assets: | ||||||||
| Leasehold improvements and equipment - net | 1,923 | 2,091 | ||||||
| Operating lease right-of-use assets - net | 3,064 | 3,613 | ||||||
| Finance lease right-of-use assets - net | 21 | 30 | ||||||
| In-process research and development | 3,017 | 3,017 | ||||||
| 1,336 | 1,336 | |||||||
| Restricted cash - security deposit | 200 | 200 | ||||||
| Total non-current assets | 9,561 | 10,287 | ||||||
| Total assets | $ | 25,104 | $ | 44,819 | ||||
| LIABILITIES AND STOCKHOLDERS’ EQUITY: | ||||||||
| Current liabilities: | ||||||||
| Accounts payable | $ | 514 | $ | 618 | ||||
| Accrued expenses and other liabilities | 1,447 | 3,099 | ||||||
| Operating lease liabilities - current | 656 | 562 | ||||||
| Financing lease liabilities - current | 5 | 7 | ||||||
| Total current liabilities | 2,622 | 4,286 | ||||||
| Non-current liabilities: | ||||||||
| Deferred tax liability | 341 | 341 | ||||||
| Operating lease liabilities - net of current portion | 2,877 | 3,533 | ||||||
| Financing lease liabilities - net of current portion | 18 | 22 | ||||||
| Total non-current liabilities | 3,236 | 3,896 | ||||||
| Total liabilities | 5,858 | 8,182 | ||||||
| Stockholders’ equity: | ||||||||
| Common stock par value | 22 | 22 | ||||||
| Additional paid-in capital | 195,018 | 190,070 | ||||||
| Accumulated deficit | (175,573 | ) | (152,631 | ) | ||||
| Accumulated other comprehensive loss | (221 | ) | (824 | ) | ||||
| Total stockholders’ equity | 19,246 | 36,637 | ||||||
| Total liabilities and stockholders’ equity | $ | 25,104 | $ | 44,819 | ||||
Consolidated Statements of Operations and Comprehensive Loss (in thousands, except share and per share data) | ||||||||
| For the Year Ended | ||||||||
| 2023 | 2022 | |||||||
| Revenue: | ||||||||
| Contract Revenue | $ | 1,096 | $ | 3,188 | ||||
| Costs and Expenses: | ||||||||
| Research and development | 14,489 | 16,678 | ||||||
| General and administrative | 10,373 | 11,100 | ||||||
| Total costs and expenses | 24,862 | 27,778 | ||||||
| Loss from operations | (23,766 | ) | (24,590 | ) | ||||
| Sale of | 484 | 3,491 | ||||||
| Other income, net | 340 | 102 | ||||||
| Net loss | $ | (22,942 | ) | $ | (20,997 | ) | ||
| Net loss per share – basic and diluted | $ | (0.11 | ) | $ | (0.10 | ) | ||
| Weighted average common shares outstanding: | ||||||||
| Basic and diluted | 217,264,526 | 216,811,439 | ||||||
| Other comprehensive gain/(loss), net of tax | ||||||||
| Unrealized gain/(loss) on securities available-for-sale | 603 | (679 | ) | |||||
| Other comprehensive gain/(loss), net of tax | 603 | (679 | ) | |||||
| Comprehensive loss | $ | (22,339 | ) | $ | (21,676 | ) | ||
2024 GlobeNewswire, Inc., source
