On
October 21, 2022, the Company announced positive interim data from the fourth and final cohort of the Phase 2 EnACT trial evaluating
the safety and efficacy of an all-oral regimen of its MAT2203 (administered with adjunctive flucytosine) product candidate (“Cohort
4”). Interim EnACT Cohort 4 data from 40 MAT2203 treatment arm participants and 40 standard of care (“SOC”) controls
will be presented on October 21, 2022 by Drs. Mucunguzi Atukunda, MBChB, MPH of the Infectious Diseases Institute of Makarere University
in Uganda and David Boulware, MD, MPH of the University of Minnesota Medical School. Cohort 4 (an all-oral treatment regimen with MAT2203)
met its prespecified primary endpoint, exceeding the target rate of cerebrospinal fluid (“CSF”) yeast clearance threshold
of >0.20 colony forming units (“CFU”) per mL of CSF per day. Overall survival in Cohort 4, a key secondary endpoint of
the study, is 95% at two weeks and currently 90% overall, with ongoing final follow-up through 18 weeks. The Company plans to initiate
a Phase 3 registration trial of MAT2203 as step-down therapy in cryptococcal meningitis in the first quarter of 2023.
Interim
Results from Cohort 4
| ● | The
CSF yeast clearance rate exceeded the prespecified primary endpoint threshold target of >0.20,
with a mean early fungicidal activity achieved of 0.30 log10 CFU/mL/day with 95%
confidence intervals from 0.22 – 0.38. |
| ● | Several
participants with high baseline fungal burdens had noteworthy antifungal activity within
the MAT2203 treatment arm, including one patient with quantitative cryptococcal culture as
high as 915,000 CFU/mL at the time of screening with effective clearance during the induction
period, a key demonstration of potent antifungal activity, even in the most challenging of
cases. |
Survival
| ● | In
40 patients receiving MAT2203 treatment, interim survival is currently 90%, while the survival
rate at Week 2 was 95%; note that Week 2 survival is the prespecified primary endpoint for
the MAT2203 Phase 3 registration trial in cryptococcal meningitis. |
Safety
| ● | MAT2203
patients had fewer Grade ≥3 Clinical Adverse Events (42%) vs. SOC treatment (59%). |
| ● | The
incidence of adverse events relating to kidney function and anemia were significantly lower
for MAT2203 compared with the SOC treatment, with no evidence of kidney toxicity seen with
six weeks of oral MAT2203 treatment. |
| ● | The
favorable safety and tolerability data seen in Cohort 4 support the use of oral MAT2203 for
longer-term use, something not previously feasible due to associated toxicities with currently
available IV formulations of amphotericin B. |
The
Company may leverage data from the EnACT trial to further the development of MAT2203 and secure multiple orphan indications for the treatment
of other life-threatening invasive fungal infections, such as mucormycosis and aspergillosis.
The
Company expects that a pivotal Phase 3 registration trial of MAT2203 in cryptococcal meningitis will be initiated early in the first
quarter of 2023 and will assess MAT2203 as step-down therapy after two loading doses of IV amphotericin B. This open-label randomized
trial, which will be partially financially supported by the National Institutes of Health National Institute of Neurological Disorders
and Stroke, involves a three arm non-inferiority design in persons living with HIV who have cryptococcal meningitis: (A) step-down therapy
with MAT2203 with treatment continuing for 2 weeks; (B) step-down therapy with MAT2203 with treatment out to 6 weeks; and (C) a SOC control
arm of IV amphotericin induction transitioning to fluconazole. The non-inferiority margin for both the primary and key secondary endpoints
will be 10% and total enrollment is planned to be approximately 270 patients, with an adaptive, de-risking design allowing for the potential
for additional patients once enrollment has reached 75%. The primary endpoint will be 2-week all-cause mortality, with a pooled analysis
across the two MAT2203 treatment arms compared with SOC control to support a potential indication for the treatment of cryptococcal meningitis.
A secondary endpoint is 10-week relapse free survival of optimized treatment (2-weeks or 6-weeks) against SOC will be evaluated for non-inferiority.
Selection of the optimal treatment regimen will be based on predefined and protocolized clinical criteria and will form the basis for
a final New Drug Application submission with the U.S. Food and Drug Administration.
Forward-
Looking Statements
This
Current Report on Form 8-K contains certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933
and Section 21E of the Securities Exchange Act of 1934 and Private Securities Litigation Reform Act, as amended, including those relating
to topline results of the ENHANCE-IT study, the Company’s strategic focus and the future development of its product candidates,
including MAT2203, the anticipated timing of regulatory submissions, the anticipated timing of clinical studies, the anticipated timing
of regulatory interactions, the Company’s ability to identify and pursue development and partnership opportunities for its products
or platform delivery technology 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.
These
statements may be identified by the use of forward-looking expressions, including, but not limited to, “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, the Company’s ability to obtain additional capital to meet its 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; the 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 SEC, including Forms 10-K, 10-Q and 8-K. Investors are cautioned not to place undue
reliance on such forward-looking statements, which speak only as of the date hereof. Except as may be required by law, the Company does
not undertake any obligation to release publicly any revisions to such forward-looking statements to reflect events or circumstances
after the date hereof or to reflect the occurrence of unanticipated events. The Company’s product candidates are all in a development
stage and are not available for sale or use.