Item 1. Business
Item 1. Business
Rezolute, Inc. (“ Rezolute ”,
the “ Company ”, “ we ” or “ us ”) is advancing targeted therapies for metabolic
diseases with serious unmet needs.
Overview
On October 9, 2020, we completed
a private placement of equity securities that resulted in net proceeds to the Company of approximately $37.6 million.
On
October 7, 2020, our Board of Directors approved a one share for 50 shares reverse stock split of our $0.001 par
value Common Stock (the “Reverse Stock Split”). The Reverse Stock Split was previously approved by stockholders
at our annual meeting on October 23, 2019 and was effective at 5:00 Eastern time on October 9, 2020. The
first day of trading after the Reverse Stock Split was on October 13, 2020. In connection with the Reverse Stock Split,
proportionate adjustments were made to increase the per share exercise prices and decrease the number of shares of Common
Stock issuable upon exercise of stock options and warrants whereby approximately the same aggregate price is required to be
paid for such securities upon exercise as had been payable immediately preceding the Reverse Stock Split. In addition, any
fractional shares that would otherwise be issued as a result of the Reverse Stock Split were rounded up to the nearest whole
share. All references in this Annual Report to the number of shares of Common Stock and the related per share amounts have
been retroactively adjusted to give effect to the Reverse Stock Split.
Also during September 2020, we made
adjustments to the composition of our Board of Directors, which included appointing Philippe Fauchet as an independent director.
Our Board now consists of a majority of independent directors.
As of the date of this Annual Report, we
continue to work diligently toward our goal of having our shares of Common Stock listed on the Nasdaq Capital Market. With the
completion of the private placement and execution of the Reverse Stock Split, and board composition adjustments discussed above,
we believe that we currently meet all of Nasdaq’s initial listing standards. We are currently engaged in active discussions
with the staff of Nasdaq with the objective to promptly complete the uplisting. However, no assurance can be provided that we will
be successful in this regard.
Summary of Clinical Assets
Our lead clinical asset, RZ358, is an antibody
therapy in Phase 2b development as a potential treatment for congenital hyperinsulinism (“CHI”), an ultra-rare pediatric
genetic disorder.
In February 2020, we announced the
initiation of the RZ358-606 Phase 2b study (“RIZE”) globally at multiple study centers. Prior to COVID-19, we had planned
to complete the RIZE study by the middle of calendar year 2021.
In
March 2020, we paused the RIZE study as a result of the COVID-19 pandemic. As the COVID-19 pandemic abates in different
regions, we are resuming clinical activities including trial site initiations. We believe that patient enrollment will recommence
by the end of October 2020. Further, if we can begin enrolling patients on this timeframe, we believe we will be able to complete
the RIZE study in the second half of calendar year 2021.
In
addition, in the first half of calendar year 2020, we had positive interactions with the U.S. Food and Drug Administration (“FDA”).
In June 2020, we announced that FDA granted us Rare Pediatric Disease (“RPD”) designation for RZ358, which qualifies
us to receive a priority review voucher upon marketing approval of the drug in CHI. Such a voucher could be redeemed to receive
a priority review of a subsequent marketing application for any drug candidate in any disease indication. Further, we submitted
the RIZE protocol to FDA which allows us to expand the study to clinical sites in the United States. We believe that patient enrollment
may commence in the United States in the first quarter of calendar year 2021.
Our next program, RZ402, is an investigational
new drug (“IND”) application-ready oral therapy, targeting diabetic macular edema (“DME”). Prior to COVID-19
we were planning to file the IND with the FDA in the third quarter of calendar year 2020, followed by the initiation and completion
of a Phase 1 study this calendar year. However, as a result of the present uncertainties associated with COVID-19 pandemic, we
have deferred filing the IND. We anticipate initiating the clinical trial for RZ402 prior to the end of the first quarter of calendar
year 2021.
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RZ358
CHI is an ultra-rare pediatric genetic
disorder characterized by excessive production of insulin by the pancreas. CHI is caused by mutations in about a dozen known genes
associated with pancreatic beta cells and their secretion of insulin. If untreated, it can lead to dangerously low blood sugar
levels. Rezolute’s lead candidate, RZ358, is an antibody in Phase 2b development that is designed to prevent severe, persistent
low blood sugar in patients with CHI.
RZ358 is an intravenously administered
human monoclonal antibody that binds to a unique site on the insulin receptor found across effector cells throughout the body in
the liver, fat, and muscle. This action allows RZ358 to counteract the effects of elevated insulin in the body. Its unique allosteric
mechanism of action is reversible, depends on both insulin levels and blood sugar levels in a dose-dependent manner, and enables
patients to achieve normal levels of insulin and glucose. Therefore, we believe that RZ358 is ideally suited as a potential therapy
for conditions characterized by excessive insulin production and it is being developed to treat hyperinsulinemia and prevent low
blood sugar for diseases such as CHI. As RZ358 acts downstream from the beta cells, across effector cells in the liver, fat, and
muscle, it may be universally effective at treating CHI caused by any of the underlying genetic defects.
The RIZE study is a multi-center, open-label,
repeat-dose Phase 2b study of RZ358 in four sequential dosing cohorts of patients with CHI who are at least two years old and have
residual low blood sugar (<70 mg/dL) that is inadequately controlled on existing therapies. In addition to safety and pharmacokinetic
evaluations, continuous glucose monitoring (“CGM”) and self-monitored blood glucose will be utilized to evaluate several
glycemic efficacy endpoints. The primary endpoint is the time within a glucose target range of 70-180 mg/dL by CGM during weeks
4 and 8 of treatment compared to baseline.
RZ402
DME is a severe complication of diabetes
marked by progressive vision loss and blindness. Consistently high blood sugar levels can cause diabetic retinopathy, a complication
characterized by damage to the blood vessels in the eye and fluid leakage into the light-sensitive tissue known as the retina.
The accumulation of fluid may lead to DME, or swelling of the macula, the part of the retina responsible for sharp, straight-ahead
vision. Currently available treatments for DME involve frequent burdensome injections into the eye or invasive laser surgery.
Rezolute is developing RZ402, a small molecule
plasma kallikrein inhibitor (“PKI”) for use in DME. As a once-daily oral investigational therapy, RZ402 is designed
to improve compliance and treatment outcomes for patients with DME. Elevated plasma levels of the enzyme kallikrein have been associated
with increased inflammation, vessel leakage and excess blood vessel growth in the eyes of patients with DME. Genetic and pharmacologic
knockout of plasma kallikrein have been shown to protect against vascular endothelial growth factor (“VEGF”) induced
retinal blood vessel leakage in murine models without damaging long-term effects.
RZ402
is a bioavailable small molecule inhibitor of plasma kallikrein that has shown the potential to prevent the onset of and reverse
vascular leakage in a dose-dependent manner in multiple rodent models of whole body and retinal vascular leakage. Target plasma
concentrations were exceeded for 24 hours following oral dosing of RZ402 in monkeys and dogs, supporting the potential for once
daily dosing in humans. Rezolute has completed a pre-IND meeting with the FDA and the IND-enabling toxicology studies in preparation
for filing an IND.
Competition
We face competition from pharmaceutical
and biotechnology companies, academic institutions, governmental agencies, and private research organizations in recruiting and
retaining highly qualified scientific personnel and consultants and in the development and acquisition of technologies.
There are a handful of companies developing
therapies for CHI that are potential competitors to RZ358. Zealand Pharma is one such company.
There are a handful of companies developing
oral therapies for diabetic macular edema that are potential competitors to the plasma kallikrein inhibitor therapy, KalVista Pharmaceuticals being one such company.
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Government Regulation
Regulation by governmental authorities
in the U.S. and other countries is a significant factor in the development, manufacture and marketing of pharmaceutical products.
All of our potential products will require regulatory approval by governmental agencies prior to commercialization. In particular,
pharmaceutical therapies are subject to rigorous preclinical testing and clinical trials and other pre-market approval requirements
by the FDA and regulatory authorities in foreign countries. Various federal, state and foreign statutes and regulations also govern
or influence the manufacturing, safety, labeling, storage, record keeping and marketing of such products.
We are also subject to various federal,
state, and local laws, regulations and recommendations relating to safe working conditions; laboratory and manufacturing practices;
the experimental use of animals; and the use and disposal of hazardous or potentially hazardous substances, including radioactive
compounds and infectious disease agents, used in connection with our research, development and manufacturing.
Research and Development
We incurred approximately $14.5 million
and $19.1 million in research and development expenses for the fiscal years ended June 30, 2020 and 2019, respectively. For
further discussion of activities related to our RZ358 and RZ402 product candidates, please refer to the discussion above. For further
discussion of our research and development expenses, please refer to the discussion under the caption Results of Operations
under Item 7 of this Annual Report.
Employees
As of June 30, 2020, we had 23 full-time
employees, all of whom have experience with pharmaceutical, biotechnology or medical product companies. None of our employees or
contractors are covered by collective bargaining agreements.
Corporate Information
We
were incorporated in Delaware in 2010. We maintain executive offices located at 201 Redwood Shores Parkway, Suite 315, Redwood
City, CA 94065 and our phone number is (650) 206-4507. Our website is located at www.rezolutebio.com . The information
contained in, or that can be accessed through, our website is not part of, and is not incorporated into this document.
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Text extracted from the filing as submitted to EDGAR. Formatting, tables and exhibits are simplified for reading; the original document is authoritative for anything you rely on.