What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2022-03-10 compared with 2021-03-29 · 440 added, 57 removed, 0 unchanged (100% of the section changed)

was formed as a blank check company incorporated on June 25, 2020 in Delaware, formed for the purpose of effecting a merger, share

exchange, asset acquisition, share purchase, reorganization or similar business combination with one or more businesses (the “business

combination”).

Until the consummation of the business combination, FSDC did not engage in any operations nor generate any

August 14, 2020, FSDC consummated its initial public offering (the “Initial Public Offering”) of 12,075,000 shares

of Class A Common Stock, generating total gross proceeds of $120,750,000.

Substantially concurrent with the consummation

of the Initial Public Offering, the Sponsor purchased 441,500 shares of Class A Common Stock (the “Private Placement

Shares”) for an aggregate purchase price of $4,415,000, or $10.00 per share.

A total of $120,750,000, comprised of the proceeds

from the Initial Public Offering and the sale of the Private Placement Shares, were placed in a U.S.-based trust account at JP

Morgan Chase Bank, N.A., maintained by Continental Stock Transfer & Trust Company, acting as trustee.

Except with respect

to interest earned on the funds held in the trust account that may be released to FS Development to pay its taxes, the proceeds

from the Initial Public Offering will not be released from the trust account until the earliest to occur of:

(i) the completion

of FSDC’s initial business combination, (ii) the redemption of the Public Shares if FSDC has not completed its initial

business combination by August 14, 2022, subject to applicable law, and (iii) the redemption of the Public Shares properly

tendered in connection with a stockholder vote to amend the current charter to modify the substance or timing of its obligation

to redeem 100% of its Public Shares if FSDC does not complete its initial business combination by August 14, 2022 or with respect

to any other provisions relating to stockholders’

rights or pre-initial business combination activity.

February 5, 2021, FSDC consummated the previously announced Business Combination.

In accordance with the terms and subject to

the conditions of the Merger Agreement, at the Effective Time of the Merger (i) all shares of Old Gemini Stock issued and outstanding

immediately prior to the Effective Time, whether vested or unvested, was converted into the right to receive their pro rata portion

of the 17,942,274 shares of Common Stock issued as Merger Consideration, provided that 2,150,000 shares of Common Stock are being

held in escrow for a period of 12 months to satisfy any indemnification obligations of Old Gemini under the Merger Agreement;

(ii) each option exercisable for Old Gemini Stock that was outstanding immediately prior to the Effective Time was assumed and

continues in full force and effect on the same terms and conditions as were previously applicable to such options, subject to

adjustments to exercise price and number of shares Common Stock issuable upon exercise based on the final conversion ratio calculated

in accordance with the Merger Agreement, and (iii) 4,264,341 shares of Common Stock were reserved for issuance under the newly

adopted 2021 Plan.

connection with the Closing, the PIPE Investors subscribed for an aggregate of 9,506,000 shares of Common Stock for an aggregate

purchase price of $95,060,000.

connection with the Business Combination, 100 shares of Class A common Stock of FSDC were redeemed at a per share purchase price

of approximately $10.00.

Upon the Closing, Gemini had 42,998,664 shares of Common Stock outstanding.

a result of the Business Combination, FSDC was renamed Gemini Therapeutics, Inc., and Old Gemini became a wholly-owned subsidiary

as otherwise expressly provided below, this report does not reflect the consummation of the business combination which, as discussed

above, occurred subsequent to the period covered hereunder.

of December 31, 2020 and prior to the business combination, we had three executive officers.

These individuals were not obligated

to devote any specific number of hours to our matters but they intended to devote as much of their time as they deemed necessary

to our affairs until we completed an initial business combination.

The amount of time they devoted in any time period varied based

on the stage of the business combination process we were in.

We had no full-time employees prior to the completion of the business

are required to file Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q with the U.S.

Securities and Exchange Commission

(the “SEC”) on a regular basis, and are required to disclose certain material events in a Current Report on Form 8-K.

The public may read and copy any materials we file with the SEC at the SEC’s Public Reference Room at 100 F Street, NE,

Washington, DC 20549.

The public may obtain information on the operation of the Public Reference Room by calling the SEC at 1-800-SEC-0330.

The SEC also maintains an Internet website that contains reports, proxy and information statements and other information regarding

issuers that file electronically with the SEC.

The SEC’s Internet website is located at http://www.sec.gov.

We are a clinical-stage precision medicine company developing novel therapeutic compounds to treat genetically defined, age-related macular degeneration (“

AMD ”) .

Our lead product candidate, GEM103, is a recombinant form of the human complement factor H protein (“

CFH ”) and is designed to address complement hyperactivity and overall dysregulation caused by loss of function mutations thus restoring retinal health in patients with AMD.

Native CFH serves multiple functions in maintaining retinal health including regulating lipid metabolism in the retina, protecting the retina against lipid and protein by-products of oxidative stress and regulating the complement system, which is part of the innate immune system.

This multifaceted regulation plays an integral role in engagement and maintenance of complement-mediated immune responses that are involved in pathogen defense and cellular debris clearance.

In January 2022, we announced that we discontinued both of our Phase 2a clinical trials of GEM103 , the ReGAtta study and the GEM103 as an Add-On to Anti-VEGF Therapy for the Treatment of Wet-AMD study.

In February 2022, we announced a corporate restructuring and that we have initiated a process to evaluate strategic alternatives.

We expect to devote substantial time and resources to exploring strategic alternatives that our board of directors believes will maximize shareholder value.

Despite devoting significant efforts to identify and evaluate potential strategic alternatives, there can be no assurance that this strategic review process will result in us pursuing any transaction or that any transaction, if pursued, will be completed on attractive terms or at all.

We have not set a timetable for completion of this strategic review process, and our board of directors has not approved a definitive course of action.

Additionally, there can be no assurances that any particular course of action, business arrangement or transaction, or series of transactions, will be pursued, successfully consummated or lead to increased stockholder value or that we will make any additional cash distributions to our stockholders.

Since inception in 2015, we have devoted substantially all our efforts and financial resources to organizing and staffing our company, business planning, raising capital, discovering product candidates and securing related intellectual property rights and conducting research and development activities for our product candidates.

We do not have any products approved for sale, and we have not generated any revenue from product sales.

We may never be able to develop or commercialize a marketable product.

To the extent we continue to pursue clinical development of GEM103, GEM307 or any other product candidate, our ability to generate revenue from product sales sufficient to achieve profitability will depend heavily on the successful development and eventual commercialization of one or more of our product candidates.

We have not yet successfully completed any pivotal clinical trials, nor have we obtained any regulatory approvals, manufactured a commercial-scale drug, or conducted sales and marketing activities.

We believe GEM103 is capable of down-regulating hyperactive complement activity while maintaining a healthy environment for the cellular architecture supporting retinal function in patients with AMD.

We believe that this differentiated approach to controlling complement dysregulation may be able to broadly address AMD pathology and potentially treat AMD.

In September 2020, we commenced a Phase 2a clinical trial of GEM103 in patients with dry AMD carrying mutations in the CFH gene, and we announced discontinuation of this trial in January 2022.

GEM103 has been granted Fast Track designation by the U.S.

Food and Drug Administration (“

FDA ”) .

Augmenting CFH activity represents a unique approach to address imbalances in the immune system in a broad array of complement-mediated inflammatory diseases.

Restoration of terminal complement pathway regulation avoids the unintended consequences of broad complement inhibition, which can result in safety issues and a reduced therapeutic index.

Integration of genetic, biological, and clinical information has identified high-risk, genetically defined subpopulations present within the current broadly defined AMD cohort.

In particular, loss of function variants in the gene that encodes CFH can reduce complement regulation and/or adversely affect retinal homeostasis, both of which strongly correlate with an increased risk for developing AMD.

AMD is a disease primarily affecting the macula, the central portion of the retina responsible for high acuity vision, and is the number one cause of irreversible blindness in the United States and Europe.

AMD has generally been characterized as either “wet”

or “dry,”

definitions driven by clinical presentation rather than underlying biology.

In dry AMD, the center of the retina slowly degenerates leading to loss of photoreceptors over time.

In wet AMD, choroidal vessels grow aberrantly and invade the retina (referred to as choroidal neovascularization (“

CNV ”) ) rapidly degrading central vision.

There are approximately 16 million AMD patients in the United States, of whom approximately 90%, or approximately 15 million, have dry AMD.

Of these, approximately six million carry a variant in the CFH gene which leads to loss of function in the CFH protein.

In these patients, CFH protein is generally expressed at normal levels but the genetic mutations result in functional insufficiency in the CFH expressed.

For wet AMD, drugs targeting one of the central proteins in CNV pathogenesis, vascular endothelial growth factor (“

VEGF ”) , have proven effective in its management.

No treatment is currently available for the approximately 15 million patients with early, intermediate, or advanced dry AMD.

We were developing GEM103 initially for the treatment of dry AMD in patients with loss of function mutations in CFH.

As a complement pathway regulatory protein, GEM103 has the potential to restore appropriate complement function by ameliorating the detrimental effects of excessive complement activation, including inappropriate cell lysis and exaggerated immune responses, while simultaneously preserving the beneficial roles of CFH, including clearance of extracellular debris and repair of oxidative damage.

The mechanism of action of GEM103 stands in contrast to that of broad complement pathway inhibitors developed to date which indiscriminately block both the detrimental and beneficial effects of complement activation.

To our knowledge, GEM103 is the first recombinant, native complement modulator that has been evaluated in human clinical trials.

GEM103 has been evaluated in a single ascending dose Phase 1 clinical trial of CFH-variant related dry AMD patients.

The findings in the Phase 1 clinical trial enabled the initiation of a Phase 2a trial evaluating multiple ascending doses in a genetically enriched patient population carrying mutation(s) in the gene for CFH and suffering from dry AMD.

Based on initial data available from the ReGAtta Phase 2a study and the Add-On to Anti-VEGF Therapy for the Treatment of Wet-AMD study , GEM103 continues to be generally well-tolerated in 510 intravitreal administrations and such preliminary data indicated rapid and sustained increased levels of CFH, supporting GEM103's biological activity to regulate complement in GA patients as indicated by a reduction in complement biomarkers elevated in patients with AMD.

In January 2022, we announced that we discontinued the ReGAtta study and the GEM103 as an Add-On to Anti-VEGF Therapy for the Treatment of Wet-AMD study.

We are also working to advance GEM307, that could be effective for treatment of systemic diseases, towards an investigational new drug application (“IND”) filing.

In January 2022, we announced that we discontinued both of our Phase 2a clinical trials of GEM103, the ReGAtta study and the GEM103 as an Add-On to Anti-VEGF Therapy for the Treatment of Wet-AMD study.

In February 2022, we announced a corporate restructuring that will result in a substantial reduction of our workforce.

In addition, we announced that we initiated a process to evaluate strategic alternatives in order to maximize shareholder value.

Introduction to AMD

AMD is a progressive and irreversible disorder of the macula.

The macula is the central portion of the retina in the eye and is responsible for both high acuity vision and color perception.

AMD may affect vision in one or both eyes and in later stages results in progressive and chronic degeneration of the macula, leading to irreversible vision loss.

AMD is a disease associated with advanced age, typically with onset occurring after the age of 50 and slowly progressing over many years.

Retinal degeneration from dry AMD is a gradual process characterized by increasing drusen deposition and other extracellular debris accumulation around retinal pigment epithelium ( “

), complement hyperactivity and subsequent loss of photoreceptor cells in the retina in proximity to the degenerated RPE.

Eventually, geographic atrophy ( “

) occurs when regions of the macula are replaced by scar tissue.

Common symptoms of dry AMD include blurry vision, loss of night vision and loss of central vision, making activities of daily living such as reading, driving and even recognizing faces progressively more difficult.

With vision being central to independent living, AMD has a large and growing societal impact as the population ages.

Dry AMD, like many complex diseases, results from the interactions between environmental and genetic risk factors.

However, unlike many late-onset conditions, approximately 70% of attributable risk for advanced AMD is explained by genetic risk.

Factors such as aging, smoking, diet and UV light exposure confer the strongest non-genetic risks.

Research over the last decade has uncovered multiple genetic variants which can increase the risk of developing advanced AMD by up to 30-fold, including many of the loci within the complement system.

One such genetic locus that occurs with high frequency and strongly increases the risk of dry AMD is the CFH gene.

We were developing GEM103, a recombinant human CFH molecule, to address the

dysregulation resulting from loss of function variants in these patients and also to restore retinal homeostasis disrupted by CFH dysfunction.

Drugs targeting VEGF, one of the key endogenous proteins driving neovascularization, have proven to be successful in the treatment of wet AMD;

however, no treatment is currently available for the remaining majority of patients with dry AMD or GA.

Current standard-of-care for dry AMD is limited to over-the-counter vitamin and antioxidant supplements, and, in the absence of available therapeutic interventions, physicians can only regularly monitor a patient’s progression toward GA, vision loss, and ultimately blindness.

There are a number of therapies in development for dry AMD and GA.

Apellis Pharmaceuticals, Inc., has announced primary efficacy results from two ongoing Phase 3 studies of pegcetacoplan targeting complement at the level of C3.

One study met its primary efficacy endpoint, and the other study did not.

Zimura, a C5 inhibitor being developed by IVERIC bio, Inc., is in pivotal clinical trials.

Lampalizumab, a complement factor D inhibitor which had been developed by F.

Hoffmann-La Roche AG failed to meet its endpoint in its Phase 3 clinical trials.

As presented publicly by that sponsor, lampalizumab failed to adequately inhibit factor D and did not have an effect on complement biomarkers of interest as assayed post hoc from in-trial aqueous humor samples.

Other approaches for the treatment of dry AMD are under investigation and in earlier stages of development such as programs from Gyroscope Therapeutics Limited and NGM Biopharmaceuticals.

Our Approach to Date

We believe that a precision medicine approach exemplified by those applied to treat cancer and cystic fibrosis, where molecular definitions of disease supplant clinical descriptions or pathological diagnoses, can also be applied to AMD.

Precision medicine is intended to more accurately diagnose patients and precisely match therapies to the underlying genetic drivers of disease.

Many well-powered and robust studies have demonstrated the significant role that genetics plays in the development of AMD and lay the groundwork for a precision approach in this large population with few options for treatment.

CLARITY Natural History Studies

In December 2018 we initiated CLARITY, a set of natural history studies designed to identify and characterize disease progression in subjects with non-central GA secondary to dry AMD who are carriers of high-risk genetic variants.

For this purpose, we developed a custom genetic test and have genetically screened more than 500 patients.

The last CLARITY study visit for the last patient occurred in July 2021.

Results confirmed the frequency of pathological genotypic mutations of interest in the dry AMD population including previously published results that approximately 80% of patients with dry AMD have a loss of function variant in the CFH gene.

The variants result in the expression of a CFH protein which is impaired in its ability to regulate complement in the eye and/or its ability to promote broader retinal health and homeostasis.

CFH, Complement and the Ocular Compartment

The immune system is composed of two distinct responses, innate and adaptive.

The complement system, as part of the innate immune system, plays an integral role in maintaining immune-surveillance and homeostasis in the ocular microenvironment.

The complement system is the first line of defense against infection and can effectively clear invading microorganisms well before activation of the adaptive immune system.

Even apart from this sentinel function, localized complement activation occurs normally within the ocular compartment and is critical to maintaining retinal health, including participating in clearing of cell debris within the retinal cell layers.

Complement dysfunction within the ocular compartment results in a diseased eye.

Complement components constitute a complex network of about 30 circulating or membrane-associated proteins, organized into hierarchal proteolytic cascades.

The complement system can be activated by three different pathways:

the classical pathway, the lectin pathway, and the alternative pathway.

The alternative pathway is constitutively activated and is highly regulated on host cells to limit damage while being amplified on non-host or severely damaged cells to provide protection from pathogens and to help clear unwanted material.

CFH provides critical functionality for retinal health.

CFH binds to markers on the surface of the body’s own cells to protect these cells from aberrant or excessive complement activity.

CFH also facilitates microbial clearance and other critical activities such as phagocytosis and lipid clearance.

In the absence of sufficient levels of functional CFH protein, cells may be permanently and terminally damaged.

CFH is a key protein that is responsible for self-surface recognition as well as maintaining a well-balanced immune response by regulating the activation of the complement system.

CFH functions physiologically to restore retinal health by both downregulating inappropriate cell lysis and facilitating clearance of extracellular debris and repair of oxidative damage which results from multiple sources.

Immunohistochemical analyses have shown that many complement components, including CFH, are molecular constituents of drusen, a type of cell debris which is a clinical hallmark of dry AMD.

Continuous control of the alternative pathway by CFH is necessary due to the amplifying properties of the alternative pathway and its potential to provoke unneeded inflammatory response if not properly controlled.

This control is best achieved by maintaining regulatory function

of the complement system by augmenting CFH activity and thereby inhibiting detrimental effects of the overly active complement system.

Our Clinical Development Program to Date

GEM103 is a full length, recombinantly produced human CFH protein which provides a functional level of active CFH in AMD patients with loss of function mutations in the gene encoding CFH.

GEM103 imparts physiologic regulation of the complement pathway driving the complement system toward equilibrium in patients where there is incomplete regulation due to insufficient functional CFH protein.

This is a unique approach to address over-activation of the innate immune system.

Preclinical and Clinical Development

A series of preclinical studies have been performed to evaluate the pharmacokinetic and pharmacodynamic performance of GEM103.

In preclinical pharmacokinetic studies, we observed that GEM103 was detected in all assayed ocular compartments, including aqueous humor, vitreous humor and the retina.

Of note GEM103 was distributed to the retina following intravitreal injection in non-human primate radio-labeled distribution studies.

Our study shows that after an intravitreal injection of radio-labelled GEM103, the protein is detected in the aqueous humor as well as into the retina, which is the site of action for the protein, for an extended period of time following a single dose.

Actions of endogenous CFH include inhibition of the complement activation cascade while permitting clearance of foreign material, cellular debris and pathogens in the eye.

In in vitro , cell-based assays, GEM103 was shown to inhibit hyperactive terminal complement activity demonstrating a more potent but comparable maximal ability to inhibit cellular lysis when compared to a broad inhibitor of C3.

In addition, we observed the necessary phagocytic activity required to clear lipid and other forms of debris is maintained by GEM103, while it is impaired by a broad inhibitor of C3, a potentially undesirable consequence of current approaches that results in complete suppression of complement activity.

In our Phase 1 clinical trial, single ascending doses of GEM103 were administered via intravitreal injection (IVT) to dry AMD patients enriched for genetic variants of interest.

GEM103 was well-tolerated across a range of single doses from 50 to 500 µg/eye in a 50 µL preparation delivered intravitreally, without any dose limiting toxicity or inflammation or anti-drug induced antibody, confirmed by an independent safety review committee.

The findings in the Phase 1 clinical trial enabled the initiation of a Phase 2a trial evaluating multiple ascending doses of 250 to 500 µg/eye GEM103 (in 50 µL) in a genetically enriched patient population carrying mutation(s) in the gene for CFH and suffering from dry AMD.

The primary objective of this study was to evaluate the safety and tolerability of monthly IVT GEM103 and provide additional information on pharmacokinetics and exploratory biomarker responses based upon serially obtained aqueous humor samples.

This study did not have a defined controlled group was not designed to inform GA efficacy.

Based on initial data available from the ReGAtta Phase 2a study and the Add-On to Anti-VEGF Therapy for the Treatment of Wet-AMD study , GEM103 continues to be generally well-tolerated through 510 intravitreal administrations with no increased risk for CNV in the GA population, no ocular serious adverse events and no study discontinuations related to GEM103.

The majority of adverse events were typical of IVT injections.

There was one report of mild inflammation related to GEM103 that resolved without treatment and did not require modification of GEM103 dosing.

Repeat IVT GEM103 dosing resulted in rapid and sustained increased levels of CFH, at least 12-fold above baseline levels with 500 µg/eye GEM103.

A regulation of complement in GA patients has been observed with ~40% reduction in Ba and ~20% reduction in C3a, complement biomarkers elevated in patients with AMD.

These initial findings support continued development and we have received feedback from the FDA through an end of Phase 2 meeting on a later stage clinical trial design to potentially support approval.

We also evaluated GEM103 as add-on therapy in patients suffering from wet AMD who have been treated with anti-VEGF therapy, as development of macular atrophy in that setting has been associated with a relative insufficiency in CFH.

In a Phase 2a clinical trial comparing 500 µg/eye GEM103 (in 50 µL) + standard of care anti-VEGF therapy (aflibercept) to sham IVT injection + standard of care anti-VEGF therapy (aflibercept), we enrolled 50 individuals and dosed every 8 weeks.

Initial results for up to 6 months of dosing showed every 8-week IVT GEM103 administration was generally well-tolerated with rapid

and sustained increased levels of CFH and regulation of complement as evidenced by reduction in complement biomarkers elevated in patients with AMD.

As previously described, in January 2022, we announced that we discontinued both of our Phase 2a clinical trials, the ReGAtta study and the GEM103 as an Add-On to Anti-VEGF Therapy for the Treatment of Wet-AMD study, as both studies have achieved their intended purpose of evaluating GEM103’s safety and tolerability.

Additional Programs

Factor H Potentiating Antibody

In addition to AMD, there are other systemic conditions that have complement dysregulation as part of the underlying disease pathologies.

Many of these conditions affect the renal system and include rare diseases such as atypical Hemolytic Urea Syndrome, C3 Glomerulopathy as well as more common disorders like IgA Nephropathy.

Many of these diseases have genetic risk factors that include CFH dysregulation and other complement regulatory proteins like the CFH-related proteins.

We have developed GEM307 as a factor H potentiating antibody that enhances the activity of endogenous CFH, effectively increasing the effective functional concentration of CFH.

We have pre-clinical data supporting improvement of clinical benefit in animal models mimicking these conditions of complement dysregulation.

We have received pre-IND feedback from the FDA.

Manufacturing

We do not currently own or operate manufacturing facilities for the production of clinical or commercial quantities of our product candidates.

We rely on well-established third-party contract manufacturing organizations (“CMOs”) to produce our product candidates, and we have recruited personnel with experience to manage the third-party CMOs producing our product candidates and other product candidates or products that we may develop in the future.

Our lead product candidate, GEM103, is a recombinant version of the endogenous CFH protein that is found most widely in our ‘intent to treat’

Specifically, it contains the amino acids V62, Y402 and E936 which are those most frequently found in the Caucasian population.

The process for manufacturing GEM103 consists of a cell culture and purification processes to achieve a stringent quality, purity, strength and safety criteria in line with a product candidate dosed intravitreally.

We have paused manufacturing of GEM103 as we engage in a process to evaluate strategic alternatives.

The process for manufacturing GEM307 consists of a cell culture and purification processes to achieve a stringent quality, purity, strength and safety criteria in line with regulatory expectations for an IND.

Sales and Marketing

We hold worldwide commercialization rights to each of our product candidates.

In order to market for sale a product, we would need to build focused capabilities to commercialize development programs for certain indications where we believe that the medical specialists for the indications are sufficiently concentrated to allow us to effectively promote the product with a targeted sales team.

In other indications, we would need to seek to enter into collaborations that we would believe might contribute to our ability to advance development and ultimately commercialize our product candidates.

We could also seek to enter into collaborations where we believe that realizing the full commercial value of our development programs would require access to broader geographic markets or the pursuit of broader patient populations or indications.

Research Collaboration and License Agreement

In April 2017, we entered into a Research Collaboration and License Agreement with Sanquin Blood Supply Foundation (“Sanquin”) (the “2017 License Agreement”) to develop antibodies that bind and enhance the activity of CFH.

From the effective date of the 2017 License Agreement until the end of April 2019, the parties engaged in a research program based on an agreed upon research plan.

The research program was overseen by a joint steering committee, comprised of two members from each of Gemini and Sanquin, with each party having one vote with respect to decisions within the purview of the joint

steering committee.

If the joint steering committee was unable to resolve any issues unanimously, then such disputes were subject to a dispute resolution procedures.

We funded Sanquin’s research during the term of the research program.

Following the conclusion of the research program, we have sole responsibility for the development of licensed products for the treatment and prevention of diseases in humans.

Sanquin granted us an exclusive royalty-bearing license, with the right to sublicense through multiple tiers, to Sanquin’s patent rights, including patent rights generated during the research program and a non-exclusive license, with the right to sublicense through multiple tiers, to Sanquin’s background know-how and materials, in each case to research, develop, commercialize, make, use, sell, offer for sale and import or otherwise exploit licensed products.

On March 7, 2022, we entered into an amendment to the 2017 License Agreement (the “2022 Amendment”) to clarify that certain patent rights directed to CFH potentiating antibodies are jointly owned by us and Sanquin.

Under the 2022 Amendment, Sanquin granted us an exclusive (even as to Sanquin) royalty-bearing license, with the right to sublicense through multiple tiers, to the portion of these patent rights owned by Sanquin.

Pursuant to the 2017 License Agreement with the 2022 Amendment incorporated (the “Amended License Agreement”), we are required to use commercially reasonable efforts to conduct development and commercialization of licensed products in accordance with an agreed upon development plan.

As consideration for the license, we paid Sanquin a one-time, non-refundable upfront payment of $100,000.

We are required to make milestone payments to Sanquin upon achievement of certain development and commercial milestones (i.e., once net sales targets exceed certain thresholds) totaling up to an aggregate amount of $29.0 million.

We are also required to pay Saquin a low double digit percentage of any non-royalty sublicensing income received and are required to make minimum royalty payments to Sanquin on each anniversary date of the effective date of the 2017 License Agreement.

We are required to make royalty payments of between 1.25% and 2.50% of net product sales if commercialization is achieved, subject to offset by minimum royalty payments due and up to 50% reduction for royalty stacking.

The Amended License Agreement shall terminate on a country-by-country and licensed product-by-licensed product basis upon the latest of (i) expiration of the last valid claim of a Sanquin patent or a jointly owned patent that covers such licensed product, (ii) seven years after the first commercial sale of such licensed product, or (iii) the date on which there is no longer any marketing exclusivity for such licensed product.

The Amended License Agreement may be terminated by either party (i) upon 90 days written notice in the event of the other party’s uncured breach of the Amended License Agreement, or (ii) the other party files for bankruptcy protection, makes an assignment for the benefit of its creditors, or files a petition for bankruptcy or insolvency that is not dismissed in 90 days.

We have the right to terminate the Amended License Agreement at any time upon 90 days prior written notice, and Sanquin has the right to terminate the Amended License Agreement if we fail to meet our diligence obligations under the Amended License Agreement.

Intellectual Property

Our success depends in part upon our ability to protect our core technology and intellectual property.

To protect our intellectual property rights, we rely on patents, trademarks, copyrights and trade secret laws, confidentiality procedures, and employee disclosure and invention assignment agreements.

Our intellectual property is critical to our business and we strive to protect it through a variety of approaches, including by obtaining and maintaining patent protection in the United States and internationally for our product candidates, novel biological discoveries, and other inventions that are important to our business.

For our product candidates, we generally intend to pursue patent protection covering compositions of matter, methods of making and methods of use, including combination therapies.

As we continue the development of our product candidates, we intend to identify additional means of obtaining patent protection that would potentially enhance commercial success, including through claims covering additional methods of use and biomarkers and complementary diagnostic and/or companion diagnostic related claims.

As of March 7, 2022, we own or exclusively license approximately 59 patents and pending patent applications in the United States (“U.S.”) and foreign jurisdictions, including one granted U.S.

patent, 11 granted foreign patents, four pending U.S.

non-provisional patent applications and 43 pending foreign patent applications.

Our patent portfolio relating to GEM103 includes two patent families owned by us.

The first patent family includes a pending Patent Cooperation Treaty (“PCT”) application directed to dosage regimens for treating inflammatory ocular diseases using GEM103 and certain biomarkers for monitoring responses to the treatment.

The statutory expiration for any U.S.

and foreign patents issuing from this family is 2041.

The second patent family includes a pending PCT application directed to methods of treating age-related macular degeneration using GEM103 in patients who carry certain CFH genetic mutations.

The statutory expiration for any U.S.

and foreign patents issuing from this family is 2040.

Our patent portfolio relating to our factor H potentiating antibody program includes two patent families that we exclusively license from Sanquin Blood Supply Foundation and one patent family that we jointly own with Sanquin.

The two in-licensed

patent families are directed to antibodies that bind the same region of the factor H protein as our GEM307 product candidate.

The first in-licensed family includes granted patents in Australia, France, Germany, Italy, the Netherlands, Mexico, Spain, and U.K.

that cover GEM307 with statutory expiration in 2035.

This family also include pending patent applications in Brazil, Canada, Israel, Japan, and South Korea which, if issued, would have statutory expiration in 2035.

The second in-licensed patent family is pending in Australia, Brazil, Canada, China, Europe, Hong Kong, Israel, Japan, the Republic of Korea, Mexico and the United States.

The statutory expiration for any patents issuing from this family is 2039.

The patent family jointly owned by us and Sanquin is directed to the specific GEM307 product candidate.

This family is pending in the United States, Argentina, Australia, Brazil, Canada, China, Europe, India, Israel, Japan, South Korea, Mexico, New Zealand, Russia, Singapore, South Africa and Taiwan.

The statutory expiration for any patents issuing from this family is 2040.

In addition to patents, we rely upon unpatented trade secrets and know-how and continuing technological innovation to develop and maintain our competitive position.

However, trade secrets and know-how can be difficult to protect.

We seek to protect our proprietary information, in part, by executing confidentiality agreements with our collaborators and scientific advisors, and non-solicitation, confidentiality, and invention assignment agreements with our employees and consultants.

We have also executed agreements requiring assignment of inventions with selected scientific advisors and collaborators.

The confidentiality agreements we enter into are designed to protect our proprietary information and the agreements or clauses requiring assignment of inventions to us are designed to grant us ownership of technologies that are developed through our relationship with the respective counterparty.

We cannot guarantee, however, that we have executed such agreements with all applicable counterparties, such agreements will not be breached, or that these agreements will afford us adequate protection of our intellectual property and proprietary rights.

For more information, see “

Risk factors —

Risks related to our intellectual property .”

The biotechnology and pharmaceutical industries are characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary products.

While we believe that our technologies, knowledge, experience and scientific resources provide us with competitive advantages, we face potential competition from many different sources, including major pharmaceutical, specialty pharmaceutical and biotechnology companies, academic institutions and governmental agencies and public and private research institutions.

Any product candidates that we successfully develop and commercialize will compete with existing therapies and new therapies that may become available in the future.

The biotechnology and pharmaceutical industries, including complement therapies, are characterized by rapidly changing technologies, competition and a strong emphasis on intellectual property.

We are aware of several companies focused on developing precision medicines in various indications that may compete with our products.

We may also face competition from large and specialty pharmaceutical and biotechnology companies, academic research institutions, government agencies and public and private research institutions with genetic medicine and other therapeutic approaches.

We consider our most direct competitors with respect to GEM103 for the treatment of AMD to be Apellis Pharmaceuticals, Inc.

and IVERIC bio.

Apellis Pharmaceuticals, Inc.

has announced primary efficacy results from two ongoing Phase 3 studies of pegcetacoplan targeting complement at the level of C3.

One study met its primary efficacy endpoint, while the other study did not.

IVERIC bio is conducting a pivotal study in geographic atrophy for its C5 inhibitor.

Other approaches are under investigation and in earlier stages of development such as programs from Gyroscope Therapeutics Limited and NGM Biopharmaceuticals.

Government Regulation

The FDA and other regulatory authorities at federal, state and local levels, as well as in foreign countries, extensively regulate, among other things, the research, development, testing, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging, storage, distribution, record keeping, approval, advertising, promotion, marketing, post-approval monitoring and post-approval reporting of biologics such as those we have been developing.

We, along with our vendors, collaboration partners, contract research organizations (“CROs”) and CMOs, would be required to navigate the various preclinical, clinical, manufacturing and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct studies or seek approval of our product candidate.

The process of obtaining regulatory approvals of drugs and ensuring subsequent compliance with appropriate federal, state, local and foreign statutes and regulations requires the expenditure of substantial time and financial resources.

In the United States, where we have initially been focusing our product development, the FDA regulates biologics under the Federal Food, Drug and Cosmetic Act (“FDCA”) and the Public Health Service Act (“PHSA”) and their implementing

Biologics are also subject to other federal, state and local statutes and regulations.

Our product candidates are early-stage and have not been approved by the FDA for marketing in the United States.

The process required by the FDA before our product candidates are approved for therapeutic indications and may be marketed in the United States generally involves the following:

completion of extensive preclinical studies in accordance with applicable regulations, including studies conducted in accordance with Good Laboratory Practice (“GLP”) requirements;

submission to the FDA of an IND which must become effective before clinical trials may begin and must be updated annually or when significant changes are made;

approval by an Institutional Review Board (“IRB”) or independent ethics committee at each clinical trial site before each trial may be initiated;

performance of adequate and well-controlled clinical trials in accordance with Good Clinical Practice (“GCP”) requirements and other clinical trial-related regulations to establish the safety, purity and potency of the proposed biological product candidate for its intended purpose;

preparation and submission to the FDA of a Biologics License Application (“BLA”) after completion of all pivotal trials;

a determination by the FDA within 60 days of its receipt of a BLA to file the application for review;

satisfactory completion of one or more FDA pre-approval inspections of the manufacturing facility or facilities where the product will be produced to assess compliance with current Good Manufacturing Practice requirements (“cGMPs”) to assure that the facilities, methods and controls are adequate to preserve the biological product’s continued safety, purity and potency;

potential FDA audit of the clinical trial sites that generated the data in support of the BLA;

payment of user fees for FDA review of the BLA;

FDA review and approval of the BLA, including consideration of the views of any FDA advisory committee, prior to any commercial marketing or sale of the biologic in the United States.

Preclinical and clinical trials for biologics

Before testing any drug or biologic in humans, the product candidate must undergo rigorous preclinical testing.

Preclinical studies include laboratory evaluations of chemistry, formulation and stability, as well as in vitro and animal studies to assess safety and in some cases to establish the rationale for therapeutic use.

The conduct of preclinical studies is subject to federal and state regulations and requirements, including GLP requirements for safety and toxicology studies.

The results of the preclinical studies, together with manufacturing information and analytical data must be submitted to the FDA as part of an IND.

An IND is a request for authorization from the FDA to administer an investigational product to humans, and it must become effective before clinical trials may begin.

The central focus of an IND submission is on the general investigational plan and the protocol(s) for clinical studies.

The IND also includes results of animal and in vitro studies assessing the toxicology, pharmacokinetics, pharmacology, and pharmacodynamic characteristics of the product;

chemistry, manufacturing, and controls information;

and any available human data or literature to support the use of the investigational product.

The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises concerns or questions about the conduct of the clinical trial, including concerns that human research subjects will be exposed to unreasonable health risks, and imposes a clinical hold.

In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin.

Some long-term preclinical testing may continue after the IND is submitted.

Accordingly, submission of an IND may or may not result in FDA authorization to begin a trial.

A separate submission to an existing IND must also be made for each successive clinical trial conducted during product development of a product candidate, and the FDA must grant permission, either explicitly or implicitly by not objecting, before each clinical trial can begin.

The clinical stage of development involves the administration of the product candidate to healthy volunteers or patients under the supervision of qualified investigators, generally physicians not employed by or under the trial sponsor’s control, in accordance with GCP requirements, which include the requirements that all research subjects provide their informed consent for their participation in any clinical trial.

Clinical trials are conducted under protocols detailing, among other things, the

objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria and the parameters and criteria to be used in monitoring safety and evaluating effectiveness.

Each protocol, and any subsequent amendments to the protocol, must be submitted to the FDA as part of the IND.

Furthermore, each clinical trial must be reviewed and approved by an IRB for each institution at which the clinical trial will be conducted to ensure that the risks to individuals participating in the clinical trials are minimized and are reasonable related to the anticipated benefits.

The IRB also approves the informed consent form that must be provided to each clinical trial subject or his or her legal representative, and must monitor the clinical trial until completed.

The FDA, the IRB, or the sponsor may suspend or discontinue a clinical trial at any time on various grounds, including a finding that the subjects are being exposed to an unacceptable health risk.

Some studies also include oversight by an independent group of qualified experts organized by the clinical study sponsor, known as a data safety monitoring board, which provides authorization for whether or not a study may move forward at designated check points based on access to certain data from the study and may halt the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy.

There also are requirements governing the reporting of ongoing clinical trials and completed clinical trials to public registries.

Information about applicable clinical trials, including clinical trials results, must be submitted within specific timeframes for publication on the www.clinicaltrials.gov website.

A sponsor who wishes to conduct a clinical trial outside of the United States may, but need not, obtain FDA authorization to conduct the clinical trial under an IND.

When a foreign clinical trial is conducted under an IND, all FDA IND requirements must be met unless waived.

Generally, the FDA will accept a well-designed and well-conducted foreign clinical study not conducted under an IND if the study was conducted in accordance with GCP requirements, and the FDA is able to validate the data through an onsite inspection if deemed necessary.

The GCP requirements encompass both ethical and data integrity standards for clinical trials.

The FDA’s regulations are intended to help ensure the protection of human subjects enrolled in non-IND foreign clinical trials, as well as the quality and integrity of the resulting data.

They further help ensure that non-IND foreign trials are conducted in a manner comparable to that required for clinical trials in the United States.

Clinical trials to evaluate therapeutic indications to support BLAs for marketing approval are typically conducted in three sequential phases, which may overlap.

Phase 1 —

Phase 1 clinical trials involve initial introduction of the investigational product into healthy human volunteers or patients with the target disease or condition.

These studies are typically designed to test the safety, dosage tolerance, absorption, metabolism and distribution of the investigational product in humans, evaluate the side effects associated with increasing doses, and, if possible, to gain early evidence of effectiveness.

Phase 2 —

Phase 2 clinical trials typically involve administration of the investigational product to a limited patient population with a specified disease or condition to evaluate the preliminary efficacy, optimal dosages and dosing schedule and to identify possible adverse side effects and safety risks.

Multiple Phase 2 clinical trials may be conducted to obtain information prior to beginning larger and more expensive Phase 3 clinical trials.

Phase 3 —

Phase 3 clinical trials typically involve administration of the investigational product to an expanded patient population to further evaluate dosage, to provide statistically significant evidence of clinical efficacy and to further test for safety, generally at multiple geographically dispersed clinical trial sites.

These clinical trials are intended to establish the overall risk/benefit ratio of the investigational product and to provide an adequate basis for product approval.

Generally, two adequate and well-controlled Phase 3 clinical trials are required by the FDA for approval of a BLA.

Post-approval trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval.

These trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication and are commonly intended to generate additional safety data regarding use of the product in a clinical setting.

In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval of a BLA.

Progress reports detailing the results of the clinical trials, among other information, must be submitted at least annually to the FDA and written IND safety reports must be submitted to the FDA and the investigators fifteen days after the trial sponsor determines the information qualifies for reporting for serious and unexpected suspected adverse events, findings from other studies or animal or in vitro testing that suggest a significant risk for human participants exposed to the biologic and any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure.

The sponsor must also notify the FDA of any unexpected fatal or life-threatening suspected adverse reaction as soon as possible but in no case later than seven calendar days after the sponsor’s initial receipt of the information.

Concurrent with clinical trials, companies usually complete additional animal studies and must also develop additional information about the biological characteristics of the product candidate and finalize a process for manufacturing the drug product in commercial quantities in accordance with cGMP requirements.

The manufacturing process must be capable of

consistently producing quality batches of the product candidate and manufacturers must develop, among other things, methods for testing the identity, strength, quality and purity of the final drug product.

Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life and to identify appropriate storage conditions for the product candidate.

BLA Submission and Review by the FDA

To the extent we continue to develop our product candidates, we could seek data exclusivity or market exclusivity for our product candidates.

Assuming successful completion of the required clinical testing, the relevant results of the pertinent preclinical studies and clinical trials, together with detailed information relating to the product’s chemistry, manufacture, controls and proposed labeling, among other things, are submitted to the FDA as part of a BLA requesting approval to market the product for one or more indications.

A BLA is a request for approval to market a new biologic for one or more specified indications.

Data may come from company-sponsored clinical trials intended to test the safety and efficacy of a product’s use or from a number of alternative sources, including studies initiated by investigators.

To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety, purity and potency of the investigational product to the satisfaction of the FDA.

FDA approval of a BLA must be obtained before a biologic may be marketed in the United States.

In addition, under the Pediatric Research Equity Act (“PREA”), a BLA or supplement to a BLA must contain data to assess the safety and effectiveness of the biological product candidate for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.

The Food and Drug Administration Safety and Innovation Act requires that a sponsor who is planning to submit a marketing application for a biological product that includes a new clinically active component, new indication, new dosage form, new dosing regimen or new route of administration submit an initial Pediatric Study Plan (PSP) within sixty days after an end-of-Phase 2 meeting or as may be agreed between the sponsor and FDA.

Unless otherwise required by regulation, PREA does not apply to any biological product for an indication for which orphan designation has been granted.

The FDA reviews all submitted BLAs before it accepts them for filing and may request additional information rather than accepting the BLA for filing.

The FDA must make a decision on accepting a BLA for filing within 60 days of receipt, and such decision could include a refusal to file by the FDA.

Once the submission is accepted for filing, the FDA begins an in-depth substantive review of the BLA.

The FDA reviews a BLA to determine, among other things, whether the product is safe, pure and potent and whether the facility in which it is manufactured, processed, packaged or held meets standards designed to assure the product’s continued safety, quality and purity.

Under the goals and polices agreed to by the FDA under the Prescription Drug User Fee Act (“PDUFA”), the FDA targets ten months, from the filing date, in which to complete its initial review of an original BLA and respond to the applicant, and six months from the filing date of an original BLA filed for priority review.

The FDA does not always meet its PDUFA goal dates for standard or priority BLAs, and the review process is often extended by FDA requests for additional information or clarification.

Further, under PDUFA, as amended, each BLA must be accompanied by a user fee, and the sponsor of an approved BLA is also subject to an annual program fee.

FDA adjusts the PDUFA user fees on an annual basis.

Fee waivers or reductions may be available in certain circumstances, including a waiver of the application fee for the first application filed by a small business.

Additionally, no user fees are assessed on BLAs for products designated as orphan drugs, unless the product also includes a non-orphan indication.

The FDA may refer an application for a biologic to an advisory committee.

An advisory committee is a panel of independent experts, including clinicians and other scientific experts, which reviews, evaluates and provides a recommendation as to whether the application should be approved and under what conditions.

The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

Before approving a BLA, the FDA typically will inspect the facility or facilities where the product is manufactured.

The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications.

Additionally, before approving a BLA, the FDA may inspect one or more clinical trial sites to assure compliance with GCP and other requirements and the integrity of the clinical data submitted to the FDA.

The FDA also may require submission of a Risk Evaluation and Mitigation Strategy (“REMS”) as a condition for approving the BLA to ensure that the benefits of the product outweigh its risks.

The REMS could include medication guides, physician communication plans, assessment plans, and/or elements to assure safe use, such as restricted distribution methods, patient registries, or other risk-minimization tools.

After evaluating the BLA and all related information, including the advisory committee recommendation, if any, and inspection reports regarding the manufacturing facilities and clinical trial sites, the FDA may issue an approval letter, or, in some cases, a Complete Response Letter.

A Complete Response Letter indicates that the review cycle of the application is complete and the application is not ready for approval.

A Complete Response Letter will usually describe all of the deficiencies that the FDA has identified in the BLA, except that where the FDA determines that the data supporting the application are inadequate to support approval, the FDA may issue the Complete Response Letter without first conducting required inspections, testing submitted product lots, and/or reviewing proposed labeling.

In issuing the Complete Response Letter, the FDA may recommend actions that the applicant might take to place the BLA in condition for approval, including requests for additional information or clarification.

Even with submission of this additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.

If and when those conditions have been met to the FDA’s satisfaction, the FDA will typically issue an approval letter.

An approval letter authorizes commercial marketing of the product with specific prescribing information for specific indications.

Even if the FDA approves a product, depending on the specific risk(s) to be addressed, the FDA may limit the approved indications for use of the product, require that contraindications, warnings or precautions be included in the product labeling, require that post-approval studies, including Phase 4 clinical trials, be conducted to further assess a product’s safety after approval, require testing and surveillance programs to monitor the product after commercialization, or impose other conditions, including distribution and use restrictions or other risk management mechanisms under a REMS, which can materially affect the potential market and profitability of the product.

The FDA may prevent or limit further marketing of a product based on the results of post-marketing studies or surveillance programs.

After approval, some types of changes to the approved product, such as adding new indications, manufacturing changes, and additional labeling claims, are subject to further testing requirements and FDA review and approval.

Expedited development and review programs for biologics

The FDA maintains several programs intended to facilitate and expedite development and review of new drugs and biologics to address unmet medical needs in the treatment of serious or life-threatening diseases or conditions.

These programs include Fast Track designation, Breakthrough Therapy designation, priority review and Accelerated Approval.

A new biologic is eligible for Fast Track designation if it is intended to treat a serious or life-threatening disease or condition and demonstrates the potential to address unmet medical needs for such disease or condition.

Fast track designation applies to the combination of the product and the specific indication for which it is being studied.

Fast Track designation provides increased opportunities for sponsor interactions with the FDA during preclinical and clinical development, in addition to the potential for rolling review once a marketing application is filed, meaning that the FDA may consider for review sections of the BLA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the BLA, the FDA agrees to accept sections of the BLA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the BLA.

In addition, a new drug or biological product may be eligible for Breakthrough Therapy designation if it is intended to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the biologic, alone or in combination with or more other drugs or biologics, may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.

Breakthrough Therapy designation provides all the features of Fast Track designation in addition to intensive guidance on an efficient development program beginning as early as Phase 1, and FDA organizational commitment to expedited development, including involvement of senior managers and experienced review staff in a cross-disciplinary review, where appropriate.

Any product submitted to the FDA for approval, including a product with Fast Track or Breakthrough Therapy designation, may also be eligible for additional FDA programs intended to expedite the review and approval process, including priority review and Accelerated Approval.

A product is eligible for priority review if it is intended to treat a serious or life-threatening disease or condition, and if approved, would provide a significant improvement in safety or effectiveness.

For original BLAs, priority review designation means the FDA’s goal is to take action on the marketing application within six months of the 60-day filing date (compared with ten months under standard review).

A product intended to treat serious or life-threatening diseases or conditions may receive Accelerated Approval upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than on irreversible morbidity or mortality which is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.

Accelerated Approval is usually contingent on a sponsor’s agreement to conduct additional post-approval studies to verify and describe the product’s clinical benefit.

The FDA may withdraw approval of a drug or biologic approved under Accelerated Approval if, for example, the sponsor fails to conduct the confirmatory trials in a timely manner or the confirmatory trial fails to verify the predicted clinical benefit of the product.

In addition, unless otherwise informed by the FDA, the FDA currently requires, as a condition for Accelerated Approval, that all advertising and promotional materials that are intended for dissemination or publication within 120 days following marketing approval be submitted to the agency for review during the pre-approval review period, and that after 120 days following marketing approval, all advertising and promotional materials must be submitted at least 30 days prior to the intended time of initial dissemination or publication.

Fast Track designation, Breakthrough Therapy designation, priority review and Accelerated Approval do not change the scientific or medical standards for approval or the quality of evidence necessary to support approval but may expedite the development or review process.

Post-approval requirements for biologics

Drugs and biologics manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to recordkeeping, periodic reporting, product sampling and distribution, product tracking and tracing, reporting of adverse experiences with the product, complying with promotion and advertising requirements, which include restrictions on promoting products for unapproved uses or patient populations (known as “off-label use”) and limitations on industry-sponsored scientific and educational activities.

Although physicians may prescribe approved products for off-label uses, manufacturers may not market or promote such uses.

The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, including not only by our employees but also by agents of ours or those speaking on our behalf, and a company that is found to have improperly promoted off-label uses may be subject to significant liability.

Failure to comply with these requirements can result in, among other things, adverse publicity, warning letters, corrective advertising and potential civil and criminal penalties, including liabilities under the False Claims Act where products carry reimbursement under federal health care programs.

Promotional materials for approved biologics must be submitted to the FDA in conjunction with their first use or first publication.

Further, if there are any modifications to the product, including changes in indications, labeling or manufacturing processes or facilities, the applicant may be required to submit and obtain FDA approval of a new BLA or BLA supplement, which may require the development of additional data or preclinical studies and clinical trials.

The FDA may impose a number of post-approval requirements as a condition of approval of a BLA.

For example, the FDA may require post-market testing, including Phase 4 clinical trials, and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization.

In addition, drug and biologics manufacturers and their subcontractors involved in the manufacture and distribution of approved products are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with ongoing regulatory requirements, including cGMP, which impose certain procedural and documentation requirements upon us and our CMOs.

Changes to the manufacturing process are strictly regulated, and, depending on the significance of the change, may require prior FDA approval before being implemented.

FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting requirements upon us and any third-party manufacturers that we may decide to use.

Manufacturers and other parties involved in the drug supply chain for prescription drug products must also comply with product tracking and tracing requirements and for notifying the FDA of counterfeit, diverted, stolen and intentionally adulterated products or products that are otherwise unfit for distribution in the United States.

Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliance with cGMP and other aspects of regulatory compliance.

Failure to comply with statutory and regulatory requirements can subject a manufacturer to possible legal or regulatory action, such as warning letters, suspension of manufacturing, product seizures, injunctions, civil penalties or criminal prosecution.

There is also a continuing, annual program fee for any marketed product.

The FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market.

Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information, requirements for post-market studies or clinical trials to assess new safety risks, or imposition of distribution or other restrictions under a REMS.

Other potential consequences include, among other things:

restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls;

safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings or other safety information about the product;

mandated modification of promotional materials and labeling and issuance of corrective information;

fines, warning letters, or untitled letters;

holds on clinical trials;

refusal of the FDA to approve applications or supplements to approved applications, or suspension or revocation of product approvals;

product seizure or detention, or refusal to permit the import or export of products;

injunctions or the imposition of civil or criminal penalties;

consent decrees, corporate integrity agreements, debarment or exclusion from federal healthcare programs.

Orphan Designation and Exclusivity

Under the Orphan Drug Act, the FDA may grant orphan drug designation (“ODD”) to a drug or biologic intended to treat a rare disease or condition, defined as a disease or condition with either a patient population of fewer than 200,000 individuals in the United States, or a patient population greater of than 200,000 individuals in the United States when there is no reasonable expectation that the cost of developing and making available the drug or biologic in the United States will be recovered from sales in the United States of that drug or biologic.

ODD must be requested before submitting a BLA.

After the FDA grants ODD, the generic identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA.

If a product that has received ODD and subsequently receives the first FDA approval for a particular clinically active component for the disease for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications, including a full BLA, to market the same biologic for the same indication for seven years from the approval of the BLA, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity or if the FDA finds that the holder of the orphan drug exclusivity has not shown that it can assure the availability of sufficient quantities of the orphan drug to meet the needs of patients with the disease or condition for which the drug was designated.

Orphan drug exclusivity does not prevent the FDA from approving a different drug or biologic for the same disease or condition, or the same drug or biologic for a different disease or condition.

Among the other benefits of ODD are tax credits for certain research and a waiver of the BLA application user fee.

A designated orphan drug may not receive orphan drug exclusivity if it is approved for a use that is broader than the indication for which it received ODD.

In addition, orphan drug exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.

Biosimilars and Exclusivity

The Affordable Care Act, signed into law in 2010, includes a subtitle called the Biologics Price Competition and Innovation Act (“BPCIA”), which created an abbreviated approval pathway for biological products that are biosimilar to or interchangeable with an FDA-licensed reference biological product.

The FDA has issued several guidance documents outlining an approach to review and approval of biosimilars.

Biosimilarity, which requires that there be no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency, can be shown through analytical studies, animal studies, and a clinical study or studies.

Interchangeability requires that a product is biosimilar to the reference product and the product must demonstrate that it can be expected to produce the same clinical results as the reference product in any given patient and, for products that are administered multiple times to an individual, the biologic and the reference biologic may be alternated or switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic.

However, complexities associated with the larger, and often more complex, structures of biological products, as well as the processes by which such products are manufactured, pose significant hurdles to implementation of the abbreviated approval pathway that are still being worked out by the FDA.

Under the BPCIA, an application for a biosimilar product may not be submitted to the FDA until four years following the date that the reference product was first licensed by the FDA.

In addition, the approval of a biosimilar product may not be made effective by the FDA until 12 years from the date on which the reference product was first licensed.

During this 12-year period of exclusivity, another company may still market a competing version of the reference product if the FDA approves a full BLA for the competing product containing that applicant’s own preclinical data and data from adequate and well-controlled clinical trials to demonstrate the safety, purity and potency of its product.

The BPCIA also created certain exclusivity periods for biosimilars approved as interchangeable products.

The BPCIA is complex and continues to be interpreted and implemented by the FDA.

In addition, government proposals have sought to reduce the 12-year reference product exclusivity period.

Other aspects of the BPCIA, some of which may impact the BPCIA exclusivity provisions, have also been the subject of recent litigation.

As a result, the ultimate impact, implementation, and regulatory interpretation of the BPCIA remain subject to significant uncertainty.

A biological product can also obtain pediatric market exclusivity in the United States.

Pediatric exclusivity, if granted, adds six months to existing exclusivity periods and patent terms.

This six-month exclusivity, which runs from the end of other exclusivity protection or patent term, may be granted based on the voluntary completion of a pediatric study in accordance with an FDA-issued “Written Request”

for such a study.

Other regulatory matters

Manufacturing, sales, promotion and other activities of product candidates following product approval, where applicable, or commercialization are also subject to regulation by numerous regulatory authorities in the United States in addition to the FDA, which may include the Centers for Medicare & Medicaid Services (“CMS”), other divisions of the Department of Health and Human Services (“HHS”), the Department of Justice, the Drug Enforcement Administration, the Consumer Product Safety Commission, the Federal Trade Commission, the Occupational Safety & Health Administration, the Environmental Protection Agency and state and local governments and governmental agencies.

Recent Developments

2022 Restructuring and Process to Evaluate Strategic Alternatives

On February 28, 2022, we announced a restructuring plan to reduce our operations to preserve financial resources, resulting in a reduction of our workforce by up to 24 positions, or approximately 80%, by the end of the second quarter of 2022.

As a result, we estimate that we will incur costs within the range of $1.6 million to $1.9 million, which are expected to consist of severance benefits for the affected employees, limited reimbursement of medical insurance premiums, outplacement services and other restructuring costs and expenses.

Additionally, we have initiated a process to evaluate strategic alternatives in order to maximize shareholder value.

There can be no assurance that this strategic review process will result in us pursuing any transaction or that any transaction, if pursued, will be completed on attractive terms or at all.

Furthermore, effective as of February 28, 2022, Georges Gemayel, Ph.D., our current Executive Chair, was appointed as interim President and Chief Executive Officer to succeed Jason Meyenburg, who has transitioned from his roles as President, CEO and Director and will continue to serve as an advisor to the Company .

Gemayel will continue to serve as the Chair of our Board.

Employees and Human Capital Resources

As of December 31, 2021, we had 33 employees, including four employees with M.D.

degrees and six employees with Ph.D.

degrees, and of whom 31 were full-time employees.

None of our employees are represented by labor unions or covered by collective bargaining agreements.

We consider the relationship with our employees to be in good standing.

We also engage consultants and contractors to supplement our permanent workforce.

We believe we offer competitive compensation (including base salary, incentive bonus, and long-term equity awards tied to the value of our stock price) and benefits packages designed to attract and reward talented individuals who possess the skills necessary to support our business objectives and assist in the achievement of our strategic goals.

We are committed to protecting our employees everywhere we operate.

We have taken additional measures during the COVID-19 pandemic, including offering COVID-19 testing, as necessary.

As of January 1, 2022, all of our employees are fully-remote workers as we are now a remote-first company that does not currently maintain a physical headquarters.

Our facilities consisted of office space in Cambridge, Massachusetts.

We terminated this lease on December 31, 2021 and no longer have any properties.

We believe that our current remote working arrangement is sufficient for our current needs.

Legal Proceedings

We are not currently subject to any material legal proceedings.

Available Information

Additional information about Gemini is available on our corporate website at https://geminitherapeutics.com/, as well as Gemini’s Investor Relations website at https://investors.geminitherapeutics.com/overview/.

We use our website to distribute company information, including financial and other material information.

We make available free of charge, on or through our website, our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K, proxy statements, beneficial ownership reports on Forms 3 and 4, as well as other filings and any amendments to these documents, as soon as reasonably practicable following the time they are electronically filed with or furnished to the SEC.

The SEC maintains an Internet website that contains reports, proxy and information statements and other information regarding issuers that file electronically with the SEC.

The SEC’s Internet website is located at http://www.sec.gov.

The content of any websites referred to in this Annual Report on Form 10-K is not incorporated by reference into this report or any other report filed with or furnished to the SEC.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business