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In addition, we have limited experience as a company and have not yet demonstrated an ability to successfully overcome many of the risks and uncertainties frequently encountered by companies in new and rapidly evolving fields, particularly in the biopharmaceutical industry.
−Removed: Only two of our product candidates, IDE397 and darovasertib (IDE196), are currently in ongoing– one Phase 1 clinical trial to evaluate IDE397 for the treatment of patients having solid tumors with MTAP deletion that we initiated in April 2021, one ongoing Phase 1 clinical trial for darovasertib conducted and controlled by Novartis and one ongoing Phase 1/2 clinical trial that we initiated in June 2019 to evaluate darovasertib in solid tumors harboring GNAQ or GNA11 hotspot mutations.
+Added: Only two of our product candidates, IDE397 and darovasertib (IDE196), are currently in ongoing clinical trials – one Phase 1 clinical trial to evaluate IDE397 for the treatment of patients having solid tumors with MTAP deletion that we initiated in April 2021, one ongoing Phase 1 clinical trial for darovasertib conducted and controlled by Novartis and one ongoing Phase 1/2 clinical trial that we initiated in June 2019 to evaluate darovasertib in solid tumors harboring GNAQ or GNA11 hotspot mutations.
We have had significant operating losses since our inception.
−Removed: Our net losses for the three months ended March 31, 2021 and March 31, 2020 were $9.0 million and $12.0 million, respectively.
−Removed: As of March 31, 2021, we had an accumulated deficit of $136.0 million.
+Added: Our net losses for the six months ended June 30, 2021 and June 30, 2020 were $20.0 million and $24.4 million, respectively.
+Added: As of June 30, 2021, we had an accumulated deficit of $147.0 million.
Substantially all of our losses have resulted from expenses incurred in connection with our research and development programs and from general and administrative costs associated with our operations.
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Preclinical studies and clinical trials and additional research and development activities will require substantial funds to complete.
−Removed: As of March 31, 2021, we had cash, cash equivalents and marketable securities of $310.4 million.
+Added: As of June 30, 2021, we had cash, cash equivalents and marketable securities of $312.4 million.
We believe that we will continue to expend substantial resources for the foreseeable future in connection with the research and development of our precision medicine target and biomarker discovery platform, clinical and preclinical product candidates, and any other future product candidates we may choose to pursue, as well as other corporate uses.
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We have no products approved for sale and our two most advanced product candidates, IDE397 and darovasertib, are in the early stages of clinical development and will require additional clinical development, regulatory review and approval in each jurisdiction in which we intend to market them, access to sufficient commercial manufacturing capacity, and significant sales and marketing efforts before we can generate any revenue from product sales.
−Removed: IDE397 is currently being evening evaluated in an ongoing Phase 1 clinical trial to evaluate IDE397 for the treatment of patients with MTAP deletion.
−Removed: Darovasertibis currently being evaluated in an ongoing Phase 1/2 clinical trial in patients having tumors with GNAQ or GNA11 hotspot mutations, that we initiated in June 2019, including the combination arm with binimetinib that we initiated in June 2020.
+Added: IDE397 is currently being evaluated in an ongoing Phase 1 clinical trial to evaluate IDE397 for the treatment of patients with MTAP deletion.
+Added: Darovasertib is currently being evaluated in an ongoing Phase 1/2 clinical trial in patients having tumors with GNAQ or GNA11 hotspot mutations, that we initiated in June 2019, including the combination arm with binimetinib that we initiated in June 2020 and the combination arm with crizotinib that we initiated in December 2020.
Darovasertib is also being tested in an earlier-initiated, ongoing Phase 1 clinical trial conducted by Novartis in patients with metastatic uveal melanoma.
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The uncertainty resulting from the use of our product candidates in combination with other therapies may make it difficult to accurately predict side effects in future clinical trials.
−Removed: To date, only one of our product candidates, darovasertib, has been tested in clinical trials, including an ongoing Phase 1 clinical trial and an ongoing Phase 1/2 clinical trial, and has been observed to be generally well tolerated, with the most common AEs reported being hypotension, GI toxicities, and fatigue.
−Removed: If unacceptable side effects arise in the further development of darovasertib, including in combination with binimetinib or crizotinib, or in the development of any of our other product candidates, we, the FDA, or the IRBs at the institutions in which the clinical trials are being conducted could suspend or terminate our clinical trials or the FDA or a comparable foreign regulatory authority could order us to cease clinical trials or deny approval of our product candidates for any or all targeted indications.
+Added: To date, only two of our product candidates, IDE397 and darovasertib, have been tested in clinical trials, including an ongoing Phase 1 clinical trial of IDE397 and an ongoing Phase 1 clinical trial and an ongoing Phase 1/2 clinical trial of darovasertib, and they have been observed to be generally well tolerated, with certain drug-related SAEs and AEs being reported for darovasertib, as monotherapy and in combination with binimetinib and in combination with crizotinib.
+Added: If unacceptable side effects arise in the further development of darovasertib, including in combination with binimetinib or crizotinib, in the further development of IDE397, or in the development of any of our other product candidates, we, the FDA, or the IRBs at the institutions in which the clinical trials are being conducted could suspend or terminate our clinical trials or the FDA or a comparable foreign regulatory authority could order us to cease clinical trials or deny approval of our product candidates for any or all targeted indications.
Treatment-related side effects could also affect patient recruitment or the ability of enrolled patients to complete any of our clinical trials or result in potential product liability claims.
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For darovasertib, our small molecule inhibitor targeting PKC in genetically-defined solid tumors having GNAQ or GNA11 mutations or other genetic alterations that activate the PKC signaling pathway, other companies are conducting research and development of potential therapies for metastatic uveal melanoma based on other targets and approaches.
−Removed: For example, Immunocore is developing IMCgp100 as monotherapy for metastatic uveal melanoma in a current Phase 3 clinical trial for patients with the HLA-A2 allele.
+Added: For example, Immunocore is developing IMCgp100 (tebentafusp) as monotherapy for metastatic uveal melanoma in a current Phase 3 clinical trial for patients with the HLA-A2 allele.
Immunocore has disclosed in regulatory filings that of the approximately 5,000 to 6,000 estimated new cases of primary uveal melanoma per annum, there is an estimated addressable patient population of 1,000 patients per annum which have metastatic uveal melanoma that are HLA-A*02:01-positive and will be eligible for treatment with tebentafusp.
For our pipeline of small molecule therapeutics based on synthetic lethality, potential competition includes established companies as well as earlier-stage emerging biotechnology companies.
−Removed: Multiple companies have been involved with research and development of PARP inhibitors, including AstraZeneca (Lynparza), Clovis (Rubraca), Tesaro (Zejula), and Pfizer (Talzenna).
+Added: Multiple companies have been involved with research and development of PARP inhibitors, including AstraZeneca (Lynparza), Clovis (Rubraca), GSK (Zejula), and Pfizer (Talzenna).
With respect to our MAT2A inhibitor for solid tumors having MTAP gene deletion, Servier is developing AG-270 in a Phase 1 clinical trial for certain advanced solid tumors or lymphoma.
−Removed: Additionally, several other early-stage companies, including Artios, Breakpoint, Cyteir, Foghorn, KSQ, MetaboMed, Mirati, NeoMed, Repare, Ryvu, Silicon, Tango and Zai Lab are performing research in synthetic lethality.
+Added: Additionally, several other early-stage companies, including Anticancer Bioscience, Artios, Breakpoint, Cyteir, Foghorn, FoRx, KSQ, MetaboMed, Mirati, NeoMed, Repare, Ribon, Ryvu, Silicon (a part of Riovant), Tango and Zai Lab are performing research in synthetic lethality.
Development decisions and data from clinical trials of our competitors may adversely impact clinical development of our product candidates, and may additionally or alternatively have a material adverse impact on our financial condition or business prospects.
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We expect to expand our development and regulatory capabilities and potentially implement sales and distribution capabilities, and as a result, we will need to increase the size of our organization, and we may experience difficulties in managing growth.
−Removed: As of March 31, 2021, we had 69 employees.
+Added: As of June 30, 2021, we had 75 employees.
We will need to continue to expand our managerial, operational, finance and other resources in order to manage our operations and clinical trials, continue our development activities, submit for regulatory approval and, if approved, commercialize our product candidates or any future product candidates.
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The governors of California and over forty other states, as well as mayors of many cities, ordered their residents to cease traveling to non-essential jobs and to curtail all unnecessary travel, and to stay in their homes as much as possible.
−Removed: As of April 2021, the coronavirus has spread to most regions of the world and the United States continues to experience significant COVID-19 outbreaks.
+Added: As of July 2021, the coronavirus has spread to most regions of the world and the United States continues to experience significant COVID-19 outbreaks, particularly in certain states.
If the current economic conditions worsen or last for an extended period of time, we will be forced to significantly scale back our business and growth plans, which could have a material adverse effect on our business, results of operations and financial condition.
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Individuals at our company or at such third parties could become ill, quarantined, or otherwise unable to work and/or travel due to health reasons or governmental restrictions.
−Removed: In response to the COVID-19 pandemic, San Mateo County, California, in which our primary office is located, has issued a “regional stay at home order” pursuant to a state order issued by the Governor of California.
−Removed: We have requested that most of our personnel, including all of our administrative employees, work remotely, restricted on-site staff to only those personnel and contractors who must perform essential activities that must be completed on-site and limited the number of staff in any given research and development laboratory.
+Added: We have requested that most of our personnel, including all of our administrative employees, work remotely, restricting on-site staff to only those personnel and contractors who perform activities that must be completed on-site.
The COVID-19 pandemic could disrupt our ability to secure supplies for our facilities and to provide personal protective equipment for our employees.
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Regulatory authorities outside the United States may adopt similar restrictions or other policy measures in response to the COVID-19 pandemic, including providing guidance regarding the conduct of clinical trials.
−Removed: If global health concerns continue to prevent the FDA or other regulatory authorities from conducting their regular inspections, reviews or other regulatory activities, it could significantly impact the ability of the FDA or other regulatory authorities to timely review and process our regulatory submissions, which could have a material adverse effect on our business.
+Added: In addition, the COVID-19 pandemic may affect the operations of the FDA and other health authorities, which could result in delays of reviews and approvals, including with respect to our product candidates.
+Added: If global health concerns continue to prevent the FDA or other regulatory authorities from conducting their regular operations, inspections, reviews or other regulatory activities, it could significantly impact the ability of the FDA or other regulatory authorities to timely review and process our regulatory submissions, which could have a material adverse effect on our business.
The evolving COVID-19 pandemic may also, directly or indirectly, impact the pace of enrollment and impose logistical and trial management constraints in current or future clinical trials.
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Similarly, our ability to recruit and retain principal investigators and site staff who, as healthcare providers, may have heightened exposure to COVID-19, may be delayed or disrupted, which may adversely impact our clinical trial operations.
−Removed: Additionally, c ertain of our CROs that support our clinical trials have personnel, including related to data management and master file management, based in India, which has experienced a recent surge in COVID-19 infections, which may adversely impact our clinical trial operations .
−Removed: While the COVID-19 pandemic did not materially adversely affect our business operations in the quarter ended March 31, 2021, economic and health conditions in the United States and across most of the globe continue to change rapidly and may materially affect us economically.
+Added: Additionally, c ertain of our CROs that support our clinical trials have personnel, including personnel related to our data management and master file management, based in India, which has experienced a recent surge in COVID-19 infections, and as a result may adversely impact our clinical trial operations .
+Added: While the COVID-19 pandemic did not materially adversely affect our business operations in the quarter ended June 30, 2021, economic and health conditions in the United States and across most of the globe continue to change rapidly and may materially affect us economically.
While the potential economic impact brought by, and the duration of, COVID-19 may be difficult to assess or predict, a continuing widespread pandemic could result in significant disruption of global financial markets, reducing our ability to access capital, which could in the future negatively affect our liquidity.
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Our competitors in both the United States and abroad, many of which have substantially greater resources and have made substantial investments in patent portfolios and competing technologies, may have applied for or obtained or may in the future apply for and obtain, patents that will prevent, limit or otherwise interfere with our ability to make, use and sell our product candidates.
−Removed: There is a substantial amount of litigation, both within and outside the United States, involving patent and other intellectual property rights in the biotechnology and pharmaceutical industries, including patent infringement lawsuits, interferences, oppositions, reexaminations, inter partes review proceedings and post-grant review proceedings before the USPTO and/or corresponding foreign patent offices.
+Added: There is a substantial amount of litigation, both within and outside the United States, involving patent and other intellectual property rights in the biotechnology and pharmaceutical industries, including patent infringement lawsuits, interferences, oppositions, reexaminations, inter partes review proceedings and post-grant review proceedings before the USPTO
+Added: and/or corresponding foreign patent offices.
Numerous third-party U.S.
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In addition, identification of third-party patent rights that may be relevant to our technology is difficult because patent searching is imperfect due to differences in terminology among patents, incomplete databases and the difficulty in assessing the meaning of patent claims.
−Removed: Although no third party has asserted a claim of patent infringement against us as of March 31, 2021, others may hold proprietary rights that could prevent darovasertib, IDE397, our other product candidates or any future product candidates from being marketed.
+Added: Although no third party has asserted a claim of patent infringement against us as of June 30, 2021, others may hold proprietary rights that could prevent darovasertib, IDE397, our other product candidates or any future product candidates from being marketed.
Any patent-related legal action against us claiming damages and seeking to enjoin commercial activities relating to our product candidates or proprietary technologies could subject us to potential liability for damages, including treble damages if we were determined to willfully infringe or attorney’s fees and costs of litigation to the party whose intellectual property rights we may be found to be infringing, and require us to obtain a license to manufacture or market darovasertib, IDE397 (if GSK does not exercise its option to obtain an exclusive license to continue development of and commercialize MAT2A products), our other product candidates or any future product candidates.
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Grounds for a validity challenge include an alleged failure to meet any of several statutory requirements, including lack of novelty, obviousness or non-enablement.
−Removed: Grounds for an unenforceability
−Removed: assertion could include an allegation that someone connected with prosecution of the patent withheld relevant information from the USPTO or made a misleading statement during prosecution.
+Added: Grounds for an unenforceability assertion could include an allegation that someone connected with prosecution of the patent withheld relevant information from the USPTO or made a misleading statement during prosecution.
Third parties may also raise similar claims before the USPTO, even outside the context of litigation.
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In addition, if any of our trade secrets were to be lawfully obtained or independently developed by a competitor, we would have no right to prevent such competitor from using that technology or information to compete with us, which could harm our competitive position.
−Removed: Despite employing the contractual and other security precautions described above, the need to share trade secrets increases the risk that such trade secrets become known by our
−Removed: competitors, are inadvertently incorporated into the technology of others, or are disclosed or used in violation of these agreements.
+Added: Despite employing the contractual and other security precautions described above, the need to share trade secrets increases the risk that such trade secrets become known by our competitors, are inadvertently incorporated into the technology of others, or are disclosed or used in violation of these agreements.
If any of these events occurs or if we otherwise lose protection for our trade secrets, the value of this information may be greatly reduced and our competitive position, business, financial condition, results of operations, and prospects would be harmed.
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If our existing stockholders sell, or indicate an intention to sell, substantial amounts of our common stock in the public market, the trading price of our common stock could decline.
−Removed: As of March 31, 2021, we have outstanding a total of 32.3 million shares of common stock, of which the holders of approximately 2.3 million shares of our common stock are entitled to rights with respect to the registration of their shares under the Securities Act.
+Added: As of June 30, 2021, we have outstanding a total of 33.0 million shares of common stock, of which the holders of approximately 2.3 million shares of our common stock are entitled to rights with respect to the registration of their shares under the Securities Act.
Registration of these shares under the Securities Act would result in the shares becoming freely tradable without restriction under the Securities Act, except for shares purchased by affiliates.
Any sales of securities by these stockholders could have a material adverse effect on the trading price of our common stock.
−Removed: In addition, as of March 31, 2021, approximately 5.4 million shares of common stock that are either subject to outstanding options or reserved for future issuance under our existing equity incentive plan will become eligible for sale in the public market to the extent permitted by the provisions of various vesting schedules, Rule 144 and Rule 701 under the Securities Act.
+Added: In addition, as of June 30, 2021, approximately 5.3 million shares of common stock that are either subject to outstanding options or reserved for future issuance under our existing equity incentive plan will become eligible for sale in the public market to the extent permitted by the provisions of various vesting schedules, Rule 144 and Rule 701 under the Securities Act.
If these additional shares of common stock are sold, or if it is perceived that they will be sold, in the public market, the trading price of our common stock could decline.
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Under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended, if a corporation undergoes an “ownership change,” generally defined as a greater than 50 percentage point change (by value) in its equity ownership by certain stockholders over a three-year period, the corporation’s ability to use its pre-change net operating loss carryforwards, or NOLs, and other pre-change tax attributes (such as research and development tax credits) to offset its post-change taxable income or tax liability may be limited.
−Removed: We have experienced ownership changes in the past and in the current year.
+Added: have experienced ownership changes in the past and in the current year.
As a result of such ownership changes, our ability to utilize certain NOLs and other tax attributes may be permanently limited as such attributes will expire unused.
We are continuing to analyze the impact of such limitation on our financial statements.
−Removed: If finalized,
−Removed: Treasury Regulations currently proposed under Section 382 of the Code may further limit our ability to utilize our pre-change NOLs or credits if we undergo a future ownership change.
+Added: If finalized, Treasury Regulations currently proposed under Section 382 of the Code may further limit our ability to utilize our pre-change NOLs or credits if we undergo a future ownership change.
We have experienced ownership changes in the past and in the current year , and we may experience ownership changes in the future and/or subsequent shifts in our stock ownership (some of which may be outside our control).
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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.