What changed in this filing

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Item 1. Business

2023-02-10 compared with 2022-02-09 · 57 added, 140 removed, 606 unchanged (25% of the section changed)

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The VOYAGE study is a randomized, double-blind, placebo-controlled, multicenter trial designed to assess the efficacy, safety and tolerability of VK2809 in patients with biopsy-confirmed NASH and fibrosis ranging from stages F1 to F3.

The study is targeting enrollment of approximately 340 patients across five treatment arms.

The primary endpoint of the study will evaluate the relative change in liver fat content, as assessed by magnetic resonance imaging, proton density fat fraction, or MRI-PDFF, from baseline to week 12 in subjects treated with VK2809 as compared to placebo.

Secondary objectives include evaluation of histologic changes assessed by hepatic biopsy after 52 weeks of dosing.

In January 2023, we announced completion of patient enrollment in the VOYAGE study and expect to report data for the study’s primary endpoint in the first half of 2023.

VK2809 has been evaluated in eight completed clinical studies, which enrolled more than 300 subjects.

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The TRß receptor is known to regulate expression of an alternative VLCFA transporter, known as ABCD2.

Various preclinical models have demonstrated that increased expression of ABCD2 can lead to normalization of VLCFA metabolism.

Various preclinical models have demonstrated that increased expression of ABCD2 can lead to

normalization of VLCFA metabolism.

Preliminary data suggest that VK0214 stimulates ABCD2 expression in an in vitro model and reduces VLCFA levels in an in vivo model of X-ALD.

In June 2021, we initiated a Phase 1b clinical trial of VK0214 in patients with X-ALD.

The Phase 1b trial is a multi-center, randomized, double-blind, placebo-controlled study in adult male patients with the adrenomyeloneuropathy, or AMN, form of X-ALD.

This trial is a multi-center, randomized, double-blind, placebo-controlled study in adult male patients with the adrenomyeloneuropathy, or AMN, form of X-ALD.

The study is initially targeting enrollment across three cohorts:

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Pending a blinded review of preliminary safety, tolerability, and pharmacokinetic data, additional dosing cohorts may be pursued.

The primary objectives of the study are to evaluate the safety and tolerability of VK0214 administered once-daily over a 28-day dosing period and to assess the efficacy of VK0214 at lowering plasma levels of VLCFAs in patients with AMN.

The secondary and exploratory objectives include an evaluation of the pharmacokinetics and pharmacodynamics of VK0214 following 28 days of dosing in this population.

In January 2022, we announced that this Phase 1b trial of VK0214 in patients with X-ALD has been placed on clinical hold by the United States Food and Drug Administration, or FDA.

The FDA has requested an additional preclinical study prior to continuing the Phase 1b trial of VK0214 in X-ALD.

The request is not due to any findings from ongoing or previously completed studies.

We expect to provide the information to the FDA in the second quarter of 2022.

In January 2022, we initiated a Phase 1 SAD and MAD clinical trial of VK2735, a novel dual agonist of the glucagon-like peptide 1, or GLP-1, and glucose-dependent insulinotropic polypeptide, or GIP, receptors.

The primary objective of the study is to evaluate the safety and tolerability of VK0214 administered once-daily over a 28-day dosing period.

Secondary and exploratory objectives include an evaluation of the pharmacokinetics and pharmacodynamics of VK0214 following 28 days of dosing in this population.

In January 2022, we announced the initiation of a Phase 1 single ascending dose, or SAD, and multiple ascending dose, or MAD, clinical trial of VK2735, a novel dual agonist of the glucagon-like peptide 1, or GLP-1, and glucose-dependent insulinotropic polypeptide, or GIP, receptors.

VK2735 is in development for the potential treatment of various metabolic disorders.

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The primary objectives of the study include evaluation of the safety and tolerability of single and multiple doses of VK2735 delivered subcutaneously and the identification of VK2735 doses suitable for further clinical development.

Study investigators will also evaluate the pharmacokinetics of single and multiple doses of VK2735.

Other clinical programs include VK5211, an orally available, non-steroidal selective androgen receptor modulator, or SARM.

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VK5211 demonstrated encouraging safety and tolerability in this study, with no drug-related SAEs reported.

Our intent is to continue to pursue partnering or licensing opportunities prior to conducting additional clinical studies.

Our intent is to continue to pursue partnering or licensing opportunities for VK5211 prior to conducting additional clinical studies.

Impact of COVID-19 Pandemic

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Clinical site initiation and patient enrollment have been, and may continue to be, delayed due to the prioritization of hospital resources toward the COVID-19 pandemic.

Some patients have not been able to, and others may not be able to, comply with clinical trial protocols if quarantines impede patient movement or interrupt healthcare services.

Similarly, any inability to recruit and retain patients and principal investigators and site staff who, as healthcare providers, may have heightened exposure to COVID-19, may adversely impact our clinical trial operations.

The severity of the impact of the COVID-19 pandemic on our business will depend on a number of factors, including, but not limited to, the duration and severity of the pandemic and the extent and severity of the impact on our service providers, suppliers, contract research organizations, or CROs, and our clinical trials, all of which are uncertain and cannot be predicted, as well as the timing, rollout and availability of vaccines worldwide and the effectiveness thereof, and the willingness of the general population to be vaccinated.

As of the date of issuance of our financial statements, the extent to which the COVID-19 pandemic may materially impact our financial condition, liquidity or results of operations is still uncertain.

The severity of the impact of the COVID-19 pandemic on our business will depend on a number of factors, including, but not limited to, the duration and severity of the pandemic and the extent and severity of the impact on our service providers, suppliers, contract research organizations, or CROs, and our clinical trials, all of which are uncertain and cannot be predicted, as well as the timing, rollout and availability of vaccines worldwide and the effectiveness thereof, and willingness of the general population to be vaccinated, and the potential emergence and spread of any new variants, including Omicron and sub-variants thereof.

As of the date of issuance of our consolidated financial statements, the extent to which the COVID-19 pandemic may materially impact our financial condition, liquidity or results of operations is still uncertain.

Our Development Pipeline

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NASH, nonalcoholic steatohepatitis;

X-ALD, X-linked adrenoleukodystrophy;

GLP-1, glucagon-like peptide 1, GIP, glucose-dependent insulinotropic polypeptide;

X-ALD, X-linked adrenoleukodystrophy.

We also have three additional programs targeting metabolic diseases and anemia.

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Secondary objectives include evaluation of histologic changes assessed by hepatic biopsy after 52 weeks of dosing.

In January 2023, we announced completion of patient enrollment in the VOYAGE study and expect to report data for the study’s primary endpoint in the first half of 2023.

VK2809 in NAFLD

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In addition, VK2809 was evaluated in five additional Phase 1 trials, evaluating the pharmacokinetics, pharmacodynamics, potential drug-drug interaction of VK2809 when co-administered with a statin, alternative dosing regimens and hepatic impairment, respectively.

Activation of the glucagon-like peptide 1 (GLP-1) receptor has been shown to decrease glucose, reduce appetite, lower body weight and improve insulin sensitivity in patients with type 2 diabetes, obesity, or both.

More recently, research efforts have explored the potential co-activation of the glucose-dependent insulinotropic peptide (GIP) receptor as a means of enhancing the therapeutic benefits of GLP-1 receptor activation.

VK2735 is a dual agonist of the GLP-1 and GIP receptors that the Company is developing for the potential treatment for various metabolic disorders.

In January 2022, we initiated a Phase 1 SAD and MAD clinical trial of VK2735.

The Phase 1 trial is a randomized, double-blind, placebo-controlled, SAD and MAD study in healthy adults.

Study investigators will also evaluate the pharmacokinetics of single and multiple doses.

VK0214 in X-linked Adrenoleukodystrophy

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Pending a blinded review of preliminary safety, tolerability, and pharmacokinetic data, additional dosing cohorts may be pursued.

The primary objectives of the study are to evaluate the safety and tolerability of VK0214 administered once-daily over a 28-day dosing period.

The primary objective of the study is to evaluate the safety and tolerability of VK0214 administered once-daily over a 28-day dosing period.

Secondary and exploratory objectives include an evaluation of the pharmacokinetics and pharmacodynamics of VK0214 following 28 days of dosing in this population.

In January 2022, we announced that this Phase 1b trial of VK0214 in patients with X-ALD has been placed on clinical hold by the United States Food and Drug Administration, or FDA.

The FDA has requested an additional preclinical study prior to continuing the Phase 1b trial of VK0214 in X-ALD.

The request is not due to any findings from ongoing or previously completed studies.

We expect to provide the information to the FDA in the second quarter of 2022.

X-ALD is a rare, often fatal condition believed to occur with an incidence of approximately one in 17,000 births.

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Patients experience a variety of symptoms, including weakness in the legs, impaired vibration sense, incontinence and impotence.

Severe motor disability, requiring the use of a wheelchair or cane, develops over a 3 to 15 year period.

Severe motor disability, requiring the use of a wheelchair or cane, develops over a three to 15-year period.

Many patients experience lower limb paralysis.

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CALD has been more commonly targeted for treatment due to its devastating effects, which are often manifested at a young age.

For these patients, the only currently effective treatment option is allogeneic hematopoietic stem cell, or HSC, transplant.

For these patients, an effective treatment option is allogeneic hematopoietic stem cell, or HSC, transplant.

In this procedure, the patient is treated with HSCs containing the properly functioning copy of the ABCD1 gene, contributed by a donor other than the patient.

Additionally, a method of ex vivo insertion of a functional copy of the ABCD1 gene via an HIV-1 based lentiviral vector into the patient’s own HSCs to correct the aberrant expression of ABCD1 in patients with CALD is also in development.

Additionally, a method of ex vivo insertion of a functional copy of the ABCD1 gene via a lentiviral vector into the patient’s own HSCs to correct the aberrant expression of ABCD1 in patients with CALD has recently been approved.

Over time with either method, as the transplanted cells grow and repopulate, a partial restoration of ABCD1 function can be achieved, leading many patients to resolution of progression in the cerebral form of the disease.

While these forms of genetic correction have also shown potential clinical benefits, there is currently no approved therapy for X-ALD.

In addition, recent data suggest that, even among successfully transplanted patients, AMN can develop.

However, recent data suggest that, even among successfully transplanted patients, AMN can develop.

We believe our thyroid receptor agonists, which have the potential to normalize metabolism of VLCFAs peripherally, and potentially centrally, may positively impact all forms of X-ALD, including the currently untreatable AMN form.

VK2735 is a dual agonist of the GLP-1 and GIP receptors that the Company is developing for the potential treatment for various metabolic disorders.

In January 2022, we initiated a Phase 1 SAD and MAD clinical trial of VK2735.

The Phase 1 trial is a randomized, double-blind, placebo-controlled, SAD and MAD study in healthy adults.

Study investigators will also evaluate the pharmacokinetics of single and multiple doses.

A SARM for Hip Fracture

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Tissue selectivity is critical in treating patients recovering from hip fracture.

These patients experience elevated rates of metabolic breakdown of muscle tissue and loss of bone mineral density, or BMD.

These patients experience elevated rates of metabolic breakdown of muscle tissue and loss of bone mineral density.

This results in a loss of muscle strength, an increased risk of additional fractures and increased mortality.

Androgens and Androgen Receptors

Androgens are important for the proper regulation of the reproductive system and play critical roles in the homeostasis of the muscular, skeletal, cardiovascular, metabolic and central nervous systems.

The most predominant androgen hormone is testosterone.

Testosterone is predominately produced in the testes in men and in the adrenal glands and ovaries in women, albeit at lower levels than in men.

Testosterone stimulates the growth of muscle and bone, also known as anabolic effects, as well as the growth of the prostate and sebaceous gland, also known as androgenic effects and, as such, testosterone is considered a non-tissue-selective androgen.

While testosterone preparations are widely used for the treatment of male hypogonadism, the androgenic activity of testosterone limits its use in women and in elderly men who have a higher risk of developing benign prostatic hyperplasia, or BPH, a benign increase in prostate size and prostate cancer.

In men, the lack of selectivity of anabolic steroids may result in side effects such as acne, hair loss and progression of BPH and/or prostate cancer.

In women, exposure to exogenous testosterone can be associated with hair growth, acne and masculinization.

Furthermore, testosterone must be administered by intramuscular injections, transdermal patches or gels.

These routes of administration can be inconvenient or associated with potential safety issues.

We believe VK5211’s selectivity, limited off-target effects and convenient route of administration may make it superior to off-label testosterone for treating hip fracture and other muscle wasting disorders.

SARMs are a class of small molecules designed to elicit the benefits of androgens on tissues such as muscle and bone, without the undesirable effects on prostate and sebaceous glands, by selectively activating androgen receptors in certain tissues.

We believe that, based on their robust activity on muscle and bone, SARMs can be used for the potential treatment of a number of diseases or disorders, including hip fracture, muscle wasting, osteoporosis, frailty and hormone deficiency in both men and women in cases where testosterone supplements or anabolic steroid treatments are ineffective or where the side effect profile is inappropriate.

Clinical Data for VK5211

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No drug-related SAEs were observed in patients receiving VK5211.

In addition to the Phase 2 clinical trial described above, VK5211 has been evaluated in three Phase 1 clinical trials.

In these trials, VK5211 was shown to be safe and well-tolerated at all doses following daily oral administration for up to 21 days.

There were no reported serious adverse events determined to be related to treatment, and no clinically significant changes in liver function tests, prostate-specific antigen, hematocrit or electrocardiogram readings were observed.

Moreover, subjects treated with VK5211 for 21 days experienced statistically significant increases in lean muscle mass, and positive dose-dependent trends in functional exercise and strength measures were consistent with anabolic activity.

The first Phase 1 clinical trial was a randomized, double-blind, placebo-controlled trial in 48 healthy male volunteers conducted in 2009.

In this clinical trial, six cohorts received an escalating single dose of VK5211 ranging from 0.1 mg to 22 mg.

The primary objective of this clinical trial was to evaluate the safety and tolerability of escalating single doses of VK5211 in healthy male subjects.

Secondary objectives of the first Phase 1 clinical trial included a determination of the pharmacokinetics, or PK, and pharmacodynamics, or PD, of single escalating doses of VK5211 in healthy male subjects.

The results showed that single doses at the levels administered were well-tolerated and no serious or severe adverse events were observed among subjects receiving VK5211.

The PD results showed dose-related decreases in total testosterone and sex-hormone binding protein, consistent with the mechanism of action of selective androgen receptor modulation.

A dose-related decrease in fasting serum high-density lipoprotein, or HDL, was also observed.

VK5211 was well-tolerated and demonstrated predictable dose-proportional increases in systemic exposure.

In a subsequent Phase 1 multiple ascending dose clinical trial, which commenced in 2010 and was completed in 2011, 76 healthy men in three cohorts were dosed daily with placebo, 0.1 mg, 0.3 mg or 1 mg of VK5211 for 21 days.

The primary objective of the second Phase 1 clinical trial for VK5211 was to assess the safety and tolerability of escalating doses of VK5211 following repeated once-daily oral administration for 21 days in healthy men.

Secondary objectives included a determination of the PK and PD of VK5211 following repeated once-daily oral administration for 21 days.

Exploratory objectives included a determination of the effects of 21 days of treatment with VK5211 on lean body mass measured by dual energy X-ray absorptiometry scan, maximal voluntary strength measured by the one repetition maximum method, and stair climbing power.

The average body mass index in all cohorts

ranged from 24.6 kg/m 2 to 27.0 kg/m 2 .

In this clinical trial, subjects receiving 1 mg doses of VK5211 demonstrated a statistically significant 1.2 kilogram average increase in lean body mass.

Positive, dose-dependent trends in strength and performance measurements were also observed.

There were no significant changes or trends in fat mass across cohorts.

VK5211 was shown to be safe and well tolerated, with a similar frequency of adverse events between the treated and placebo groups.

There were no drug-related serious adverse events.

In addition, there were no significant changes in hemoglobin, prostate-specific antigen, liver function tests or QT interval at any dose.

VK5211 also displayed a favorable pharmacokinetic profile, without any changes in prostate-specific antigen.

In September 2015, we completed a Phase 1 clinical trial of VK5211 in 24 healthy male and female subjects aged 65 and over.

Subjects received once-daily oral doses of VK5211 for seven days.

The results of this study showed VK5211 to be safe and well-tolerated, with predictable pharmacokinetic properties.

VK5211 Summary Characteristics

Based on the Phase 2 trial, the three Phase 1 trials, and additional preclinical data, we believe VK5211 has the following important characteristics that may suggest therapeutic benefits in patients recovering from hip fracture surgery:

Improvement in lean body mass:

Clinical data to date suggests VK5211 rapidly stimulates the formation of lean body mass, or LBM, an important property for the hip fracture recovery setting, where patients can lose up to 6% of lean body mass in the two months following injury.

Improvement in bone growth and density:

VK5211 has demonstrated encouraging efficacy in a standard animal model of osteoporosis, demonstrating improved bone mineral content, density and strength.

This may benefit patients following hip surgery, where loss of bone mineral density can exceed 12 times the background rate for patients with osteoporosis.

Encouraging tolerability:

VK5211 has been well-tolerated at and above doses that we administered in our Phase 2 clinical trial.

Novel mechanism of action:

Based on the anabolic characteristics imparted by selective activation of the androgen receptor, we believe VK5211 may stimulate bone and muscle growth, without demonstrating adverse bone remodeling properties that are a potential concern for osteoporosis drugs such as bisphosphonates.

We expect VK5211’s novel mechanism of action to provide critical bone and muscle growth promoting advantages.

Once-daily, oral convenience:

Clinical data suggest that VK5211 has the potential to provide therapeutic benefits via once-daily oral dosing.

This may represent an important advantage among elderly patients, relative to injectable protein or bisphosphonate therapies.

Hip Fracture and Other Muscle Wasting Market Opportunities

More than 300,000 patients in the U.S.

experience hip fractures each year, and approximately 50% lose the ability to live independently following the injury.

The number of hip fractures is expected to grow in the U.S.

as the population ages.

Due to required limitations in mobility following hip fracture, patients experience muscle atrophy, or deterioration from lack of use, which impacts the time required for rehabilitation to restore physical function.

We believe VK5211’s potential stimulatory effect on lean body mass could result in benefits to patients recovering from hip fracture or other conditions requiring orthopedic intervention, such as hip or knee replacement surgery.

Currently, there are no approved therapies to assist in the maintenance or restoration of LBM, BMD or restoration of functional performance for these patients.

Hip fracture in the elderly is a serious and debilitating condition with a high mortality rate.

One year mortality in this group is estimated to range from 20% to 30% and an estimated 50% of patients lose the ability to walk independently.

As a result of the loss of mobility, and additional morbidities caused by the hip fracture, 20% of patients will require stays at long-term care facilities.

Studies show that following hip fracture, patients experience a severe and rapid decline in LBM and BMD.

These reported rates of decline are 12 to 75 times the rates observed in persons of similar age and demographics who have not sustained a hip fracture.

Loss of LBM is believed to contribute to morbidity, disability and risk of re-fracture in hip fracture patients.

Loss of BMD is associated with an increased risk of mortality and re-fracture.

Our intent is to continue to pursue partnering or licensing opportunities for VK5211 prior to conducting additional clinical studies.

Three Pipeline Programs Target Metabolic Disease with Large Unmet Medical Need

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The key competitive factors affecting the success of each of our drug candidates, if approved, are likely to be its efficacy, safety, tolerability, frequency and route of administration, convenience and price, the level of branded and generic competition and the availability of coverage and reimbursement from government and other third-party payors.

While no therapies are currently approved for the treatment of non-alcoholic steatohepatitis, we are aware of numerous development-stage programs targeting this disease, including obeticholic acid from Intercept Pharmaceuticals, Inc., resmetirom (MGL-3196) from Madrigal Pharmaceuticals, Inc., arachidyl amido cholanoic acid from Galmed Pharmaceuticals Ltd., belapectin (GR-MD-02) from Galectin Therapeutics Inc., lanifibranor from Inventiva S.A., semaglutide from Novo Nordisk A/S, tesamorelin from Theratechnologies Inc., firsocostat (GS-0976) and cilofexor (GS-9674) from Gilead Sciences, Inc., tropifexor and licogliflozin from Novartis Pharmaceuticals Corporation, tirzepatide from Eli Lilly and Company, RG7992 (BFKB8488A) from F.

Hoffmann-La Roche AG, ervogastat (PF-06865571) and clesacostat (PF-05221304) from Pfizer Inc., MK-3655 (NGM313) from Merck & Co., Inc., efruxifermin (AKR-001) from Akero Therapeutics, Inc., pegozafermin (BIO89-100) from 89bio, Inc., and TVB-2640 from Sagimet Biosciences Inc.

In addition, we are aware of active programs at Altimmune, Inc., Arrowhead Pharmaceuticals, Inc., Ascletis Biopharmaceutical, AstraZeneca PLC, Axcella Health Inc., Boehringer Ingelheim International GmbH, Boston Pharmaceuticals Inc., Bristol Myers Squibb, Can-Fite BioPharma Ltd., Carmot Therapeutics, Inc., ChemomAb Ltd., CohBar, Inc., Corcept Therapeutics Inc., CytoDyn Inc., D&D Pharmatech, Inc., Durect Corporation, Enyo Pharma SA, Inc., GlaxoSmithKline

plc., Hanmi Pharmaceutical Co., Ltd., Hepion Pharmaceuticals, Inc., HighTide Therapeutics Inc., Ionis Pharmaceuticals, Inc., Kowa Company, Ltd., Lipocine Inc., MediciNova Inc., NorthSea Therapeutics B.V., NuSirt Biopharma, Inc., Poxel SA, Terns Pharmaceuticals, Inc., Yuhan Corporation and Cadila Healthcare Limited (a.k.a.

While no therapies are currently approved for the treatment of non-alcoholic steatohepatitis, we are aware of numerous development-stage programs targeting this disease, including obeticholic acid from Intercept Pharmaceuticals, Inc., resmetirom (MGL-3196) from Madrigal Pharmaceuticals, Inc., arachidyl amido cholanoic acid from Galmed Pharmaceuticals Ltd., belapectin (GR-MD-02) from Galectin Therapeutics Inc., lanifibranor from Inventiva S.A., semaglutide from Novo Nordisk A/S, firsocostat (GS-0976) and cilofexor (GS-9674) from Gilead Sciences, Inc., tirzepatide from Eli Lilly and Company, ervogastat (PF-06865571) and clesacostat (PF-05221304) from Pfizer Inc., MK-6024 ( efinopegdutide ) from Merck & Co., Inc., efruxifermin (AKR-001) from Akero Therapeutics, Inc., pegozafermin (BIO89-100) from 89bio, Inc., denifanstat (TVB-2640) from Sagimet Biosciences Inc., cotadutide from AstraZeneca PLC, and GSK4532990 (ARO-HSD) from GlaxoSmithKline plc.

In addition, we are aware of active programs at Aligos Therapeutics, Inc., Alnylam Pharmaceuticals, Inc., Altimmune , Inc., Arrowhead Pharmaceuticals, Inc., Ascletis Biopharmaceutical, Boehringer Ingelheim International GmbH, Boston Pharmaceuticals Inc., Bristol Myers Squibb, Can- Fite BioPharma Ltd., ChemomAb Ltd., CohBar , Inc., Corcept Therapeutics Inc., CytoDyn Inc., D&D Pharmatech , Inc., Durect Corporation, Enyo Pharma SA, Inc., Future Medicine Co., Ltd., Galecto , Inc., Gelesis Holdings Inc., Hanmi Pharmaceutical Co., Ltd., Hepagene Therapeutics, Inc., Hepion Pharmaceuticals, Inc., HighTide Therapeutics Inc., Ionis Pharmaceuticals, Inc., Johnson & Johnson, Kowa Company, Ltd., MediciNova Inc., NGM Biopharmaceuticals, Inc., NorthSea Therapeutics BV, Novartis Pharmaceuticals Corporation, Poxel SA, Regeneron Pharmaceuticals Inc., Rivus Pharmaceuticals Inc., Seal Rock Therapeutics, Inc., Terns Pharmaceuticals, Inc., Theratechnologies Inc., Yuhan Corporation, and Cadila Healthcare Limited (a.k.a.

Zydus Cadila ).

In the U.S., there are currently no marketed therapies for the maintenance or improvement of lean body mass, bone mineral density or physical function in patients recovering from non-elective hip fracture surgery.

However, VK5211, if approved, will face competition from experimental therapies that are in various stages of clinical development for conditions characterized by muscle wasting by companies including Biophytis SA, Helsinn Group and Pluristem Therapeutics Inc.

(formerly Pluristem Therapeutics Inc.).

In addition, nutritional and growth hormone-based therapies are sometimes used in patients experiencing muscle wasting.

In the U.S., there are currently no marketed therapies for the treatment of X-ALD.

Hematopoietic stem cell therapy has been used to treat cerebral X-ALD (CALD), the most severe form of the disease.

More recently, gene therapy has been shown to be effective in treating CALD, as well as elivaldogene autotemcel from bluebird bio, Inc., which has been approved by the European Commission for patients less than 18 years of age with early CALD without a matched sibling donor.

However, both treatments are invasive, requiring surgical intervention, and these do not appear to have an effect on the most pervasive form of X-ALD, AMN.

There are several experimental therapies that are in various stages of clinical development for X-ALD by companies, including Autobahn Therapeutics, Minoryx Therapeutics S.L., Neuralgene, Orpheris, Inc., Poxel SA, and SwanBio Therapeutics, Inc., which may be competitive with VK0214, if approved.

Hematopoietic stem cell therapy has been used to treat the most severe form of X-ALD, cerebral adrenoleukodystrophy, or CALD.

More recently, gene therapy has been shown to be effective in CALD, and elivaldogene autotemcel from bluebird bio, Inc.

has received accelerated approval by the FDA (to slow the progression of neurologic dysfunction in boys 4-17 years of age with early, active CALD), and approval by the European Commission (for patients less than 18 years of age with early CALD without a matched sibling donor).

However, both treatments are invasive, requiring surgical intervention, and these do not appear to have an effect on the most pervasive form of X-ALD, adrenomyeloneuropathy, or AMN.

There are several experimental therapies that are in various stages of clinical development for X-ALD by companies, including Minoryx Therapeutics S.L., Poxel SA, and SwanBio Therapeutics, Inc., which may be competitive with VK0214, if approved.

Manufacturing and Supply

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Most of our programs are based on small molecules licensed from Ligand pursuant to our Master License Agreement with Ligand, which we entered into on May 21, 2014.

We have developed additional programs ourselves, including VK2735 and others.

Agreements with Ligand

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The Voting Agreement will terminate under the same circumstances in which the Management Rights Letter will terminate.

Registration Rights Agreement

As a condition to the parties entering into the Master License Agreement, we entered into a Registration Rights Agreement, dated May 21, 2014, as amended on January 22, 2016, with Ligand, or the Registration Rights Agreement, pursuant to which we granted certain registration rights to Ligand with respect to (1) the securities issued by us to Ligand pursuant to the Master License Agreement and the securities issuable by us to Ligand pursuant to a Secured Convertible Promissory Note previously issued by us to Ligand, or, collectively, the Viking Securities, (2) the shares of our common stock issued or issuable upon conversion of the Viking Securities, if applicable, and (3) the shares of our common stock issued as a dividend or other distribution with respect to, in exchange for or in replacement of the Viking Securities, or, collectively, the Registrable Securities.

Mandatory Resale Registration Rights

Pursuant to the Registration Rights Agreement, on February 14, 2017, we filed a Registration Statement on Form S-3 under the Securities Act of 1933, as amended, or the Securities Act, covering the resale of the full amount of the Registrable Securities.

If, on any day after the Registration Statement is declared effective by the SEC Staff, sales of all of the Registrable Securities required to be included in the Registration Statement cannot be made pursuant to the Registration Statement, then we will, subject to certain exceptions, be obligated to pay to Ligand an amount in cash equal to 1% of the aggregate value of the Registrable Securities, measured as of the date of their issuance, on the day of such failure or ineffectiveness of, or inability to use, the Registration Statement and on every thirtieth day thereafter (pro-rated for partial periods) until such failure or ineffectiveness of, or inability to use, the Registration Statement is cured;

up to a maximum of 5% of the aggregate value of the Registrable Securities, measured as of the date of their issuance.

Pursuant to the terms of the Registration Rights Agreement, we also agreed to use our commercially reasonable efforts to keep each Registration Statement filed pursuant to the agreement effective with respect to all Registrable Securities until the earlier of (1) the date on which all shares of Registrable Securities may immediately be sold under Rule 144, as promulgated by the SEC under the Securities Act, or Rule 144, during any 90-day period, or (2) the date on which all of the Registrable Securities covered by the Registration Statement that are held by Ligand are sold.

Additionally, we have the right during certain periods after the effective date of the Registration Statement covering the resale of the Registrable Securities, to delay the disclosure of material, non-public information if, in the good faith opinion of our board of directors, it is not in our best interests to disclose the information.

In addition, we have the ability to prohibit sales under the Registration Statement during certain periods, subject to certain limitations.

Government Regulation

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During Phase 1 clinical trials, sufficient information about the investigational drug’s pharmacokinetics and pharmacologic effects may be obtained to permit the design of well-controlled and scientifically valid Phase 2 clinical trials.

Phase 2 – clinical trials are conducted to evaluate the effectiveness of the drug for a particular indication or in a limited number of patients in the target population to identify possible adverse effects and safety risks, to determine the efficacy of the product for specific targeted diseases and to determine dosage tolerance and optimal dosage.

of the product for specific targeted diseases and to determine dosage tolerance and optimal dosage.

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

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The FDA reviews all NDAs submitted to ensure that they are sufficiently complete for substantive review before it accepts them for filing.

It may request additional information rather than accept an NDA for filing.

It may request additional information rather than accept an NDA for

In this event, the NDA must be resubmitted with the additional information.

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Before approving an NDA, the FDA typically will inspect the facilities at which the product is manufactured.

The FDA will not approve the product 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.

The FDA will not approve the product 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 an NDA, the FDA may inspect one or more clinical sites to assure compliance with GCP regulations.

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In seeking approval for a drug through an NDA, applicants are required to list with the FDA each patent whose claims cover the applicant’s product.

Upon approval of a drug, each of the patents listed by the NDA holder listed in the drug’s application or otherwise are then published in the FDA’s Orange Book.

Upon approval of a drug, each of the patents listed by the NDA holder listed in the drug’s application or otherwise is then published in the FDA’s Orange Book.

Drugs listed in the Orange Book can, in turn, be cited by potential generic competitors in support of approval of an abbreviated new drug application, or ANDA.

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A drug is a new chemical entity if the FDA has not previously approved any other new drug containing the same active moiety, which is the molecule or ion responsible for the action of the drug substance.

During the exclusivity period, the FDA may not accept for review an ANDA or a 505(b)(2) NDA submitted by another company for another version of such drug where the

applicant does not own or have a legal right of reference to all the data required for approval.

During the exclusivity period, the FDA may not accept for review an ANDA or a 505(b)(2) NDA submitted by another company for another version of such drug where the applicant does not own or have a legal right of reference to all the data required for approval.

However, an application may be submitted after four years if it contains a Paragraph IV certification.

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NDA holders using contract manufacturers, laboratories or packagers are responsible for the selection and monitoring of qualified firms and, in certain circumstances, qualified suppliers to these firms.

These firms and, where applicable, their suppliers are subject to inspections by the FDA at any time, and the discovery of violative conditions, including failure to conform to cGMP, could result in enforcement actions that interrupt the operation of any such product or may result in restrictions on a product, manufacturer, or holder of an approved NDA, including, among other things, recall or withdrawal of the product from the market.

These firms and, where applicable, their suppliers are subject to inspections by the

FDA at any time, and the discovery of violative conditions, including failure to conform to cGMP, could result in enforcement actions that interrupt the operation of any such product or may result in restrictions on a product, manufacturer, or holder of an approved NDA, including, among other things, recall or withdrawal of the product from the market.

The FDA also may require post-marketing testing, also known as Phase 4 testing, REMS to monitor the effects of an approved product or place conditions on an approval that could restrict the distribution or use of the product.

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Department of Health and Human Services ( e.g.

, the Office of Inspector General), the Drug Enforcement Administration, the Consumer Product Safety Commission, the Federal Trade Commission, the Occupational

Safety & Health Administration, the Environmental Protection Agency, state Attorneys General and other state and local government agencies.

, the Office of Inspector General), the Drug Enforcement Administration, the Consumer Product Safety Commission, the Federal Trade Commission, the Occupational Safety & Health Administration, the Environmental Protection Agency, state Attorneys General and other state and local government agencies.

For example, sales, marketing and scientific/educational grant programs must comply with the federal Anti-Kickback Statute, the federal False Claims Act of 1986, as amended, or the federal False Claims Act, the privacy regulations promulgated under the Health Insurance Portability and Accountability Act of 1996, as amended, or HIPAA, and similar state laws.

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For example, pharmaceutical companies have been found liable under the federal False Claims Act in connection with their off-label promotion of drugs.

Penalties for a federal False Claims Act violation include three times the actual damages sustained by the government, plus mandatory civil penalties effective as of December 12, 2021 of between $11,803 and $23,607 for each separate false claim (each of which is subject to adjustment for inflation), the potential for exclusion from participation in federal healthcare programs and, although the federal False Claims Act is a civil statute, conduct that results in a federal False Claims Act violation may also implicate various federal criminal statutes.

Penalties for a federal False Claims Act violation include three times the actual damages sustained by the government, plus mandatory civil penalties effective as of May 9, 2022 of between $12,537 and $25,076 for each separate false claim (each of which is subject to adjustment for inflation), the potential for exclusion from participation in federal healthcare programs and, although the federal False Claims Act is a civil statute, conduct that results in a federal False Claims Act violation may also implicate various federal criminal statutes.

If the government were to allege that we were, or convict us of, violating these false claims laws, we could be subject to a substantial fine and may suffer a decline in our stock price.

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For example, on December 22, 2017, the Tax Cuts and Jobs Act of 2017 was signed into law, which, among other things, eliminated the individual mandate requiring most Americans (other than those who qualify for a hardship exemption) to carry a minimum level of health coverage, effective January 1, 2019.

President Biden and his administration have announced plans to amend the PPACA to, among other things, expand the scope of the law.

President Biden and his administration have announced plans to amend the PPACA to,

among other things, expand the scope of the law.

We cannot predict the ultimate form or timing of any repeal, replacement, amendment, expansion or other modification of the PPACA or the effect such a repeal, replacement, amendment, expansion or other modification would have on our business.

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A Written Request may include studies for indications that are not currently in the labeling if the FDA determines that such information will benefit the public health.

The FDA will accept the reports upon its determination that the studies were conducted in accordance with, and are responsive to, the

original Written Request or commonly accepted scientific principles, as appropriate, and that the reports comply with the FDA’s filing requirements.

The FDA will accept the reports upon its determination that the studies were conducted in accordance with, and are responsive to, the original Written Request or commonly accepted scientific principles, as appropriate, and that the reports comply with the FDA’s filing requirements.

Under the Pediatric Research Equity Act of 2003, or the PREA, an NDA or supplement thereto must contain data that is adequate to assess the safety and effectiveness of the drug product 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.

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and other foreign jurisdictions on our clinical and preclinical programs.

Information regarding the issued patents and pending patent applications, as of December 31, 2021, are as follows:

Information regarding the issued patents and pending patent applications, as of December 31, 2022, is as follows:

Subject Matter/Compounds

Geographical Scope

U.S., Australia, Canada, China, Japan, Korea, Hong Kong, Mexico, Brazil, India, Russia, New Zealand, South Africa, Europe and PCT

U.S., Australia, Canada, China, Japan, Korea, Hong Kong, Mexico, Brazil, Russia, New Zealand, South Africa, Europe and PCT

VK5211 (SARM)

U.S., Australia, Europe, Chile, Argentina, Brazil, Canada, China, India, Japan, Korea, Mexico, New Zealand, South Africa, Taiwan and Venezuela

U.S., Canada, India, Japan, Korea, Mexico, Australia, China, New Zealand, Argentina, Brazil, Europe, and Israel

U.S., Japan, Korea, Argentina and Israel

VK0612 (FBPase inhibitor)

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We have included our website address in this Annual Report on Form 10-K solely as an inactive textual reference.

As of December 31, 2021, we had seventeen full-time employees and one part-time employee, seven of whom hold a Ph.D.

Employees & Human Capital

As of December 31, 2022, we had twenty-one full-time employees, seven of whom hold a Ph.D.

All employees are engaged in research and development, business development and finance.

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We consider our relationship with our employees to be good.

Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and new employees.

The principal purposes of our equity incentive plans are to attract, retain and motivate selected employees, consultants and directors through the granting of stock-based compensation awards.

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