What changed in this filing

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Item 2. Management’s Discussion and Analysis

2021-08-10 compared with 2021-05-10 · 114 added, 113 removed, 352 unchanged (39% of the section changed)

Management’s Discussion and Analysis o f Financial Condition and Results of Operations.

Management’s Discussion and Analysis of Financial Condition and Results of Operations.

The following discussion and analysis of our financial condition and results of operations should be read in conjunction with our financial statements and related notes appearing elsewhere in this Quarterly Report on Form 10-Q.

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Because of this enhanced dependence, loss of MTAP results in synthetic lethality when MAT2A is pharmacologically inhibited.

The prevalence of MTAP deletions is estimated to be approximately 15% of all human tumors, translating to an estimated addressable population in major market countries, consisting of the US, EU5 and Japan, for patients having solid tumors with MTAP deletion to be approximately 75,000 annually.

We have initiated a Phase 1 clinical trial, designated as IDE397-001 (ClinicalTrials.gov Identifier:

The prevalence of MTAP deletions is estimated to be approximately 15% of human tumors, translating to an estimated addressable population in major market countries, consisting of the US, EU5 and Japan, for patients having solid tumors with MTAP deletion to be approximately 75,000 annually.

We are actively enrolling patients into the dose escalation and tumor biopsy cohorts of a Phase 1 clinical trial, designated as IDE397-001 (ClinicalTrials.gov Identifier:

NCT04794699) to evaluate IDE397 under an investigational new drug application, or IND.

We have dosed IDE397 into a first patient and completed enrollment into a first dose escalation cohort of this Phase 1 clinical trial.

As of June 25, 2021, we have enrolled patients in the IDE397 clinical trial having multiple solid tumor types with MTAP-deletion, including non-small cell lung cancer, pancreatic cancer, thymic cancer and adenoid cystic carcinoma.

As of June 25, 2021, IDE397 has been generally well tolerated with only grade 1 drug-related adverse events, including onstipation, nausea and fatigue;

there were no reported drug-related serious adverse events and no reported myelosuppression, or changes to bilirubin or to aminotransaminase (AST) or alanine aminotransferase (ALT) enzymes.

Our initial clinical development plans to evaluate IDE397 include a dose escalation portion of the Phase 1 clinical trial in which we are enrolling patients having solid tumors with MTAP deletion identified by commercial or institutional next generation sequencing, or NGS, panels or by MTAP immunohistochemistry, or IHC, assay with confirmation by NGS.

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Potential solid tumors we are considering for future evaluation in one or more expansion arm(s) of the clinical trial evaluating IDE397 include non-small cell lung cancer, or NSCLC, head and neck cancer, bladder cancer, gastric cancer, pancreatic cancer and esophageal cancer, among others.

We plan to obtain patient biopsies from the dose escalation and expansion portions of the clinical trial for translational research, including evaluation of certain pharmacodynamic, or PD, biomarkers, such as peripheral S-adenosyl methionine, or SAM, and tumor SAM as well as tumor symmetric dimethylarginine, or SDMA.

We have a program objective to obtain preliminary clinical PD data from the dose-escalation portion of the IDE397 monotherapy Phase 1 clinical trial in the second half of 2021.

We observed a reduction in plasma S-adenosylmethionine, or SAM, a proximal pharmacodynamic marker, in each of the first two cohorts of the IDE397 Phase 1 dose escalation study, satisfying the clinical protocol threshold of approximately 60% or greater to initiate the tumor biopsy cohort of the IDE397 Phase 1 clinical trial to evaluate tumor pharmacodynamic, or PD, biomarkers.

The clinical protocol threshold was established based on IDE397 preclinical in vivo efficacy data in MTAP-deletion xenograft models.

We plan to obtain patient biopsies for translational research from the dose escalation and expansion portions of the clinical trial, including evaluation of certain pharmacodynamic, or PD, biomarkers, such as plasma SAM and tumor SAM as well as tumor symmetric dimethylarginine, or SDMA.

We are targeting initiation of the tumor biopsy cohort in the third quarter of 2021 to evaluate tumor pharmacodynamic, or PD, biomarkers, and have a program objective to obtain tumor PD data, including tumor SAM and tumor SDMA, in the fourth quarter of 2021.

We are leading research and development of IDE397 through early clinical development, in collaboration with GlaxoSmithKline pursuant to the Collaboration, Option and License Agreement, or the GSK Collaboration Agreement, with an affiliate of GlaxoSmithKline, GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.

4), Limited, or GSK.

We expect that the PD data to be obtained from the IDE397 tumor biopsy cohort will support an option data package for review by GSK in consideration of whether to exercise its option to develop IDE397.

The GSK option is exercisable within a certain period after we deliver a data package comprising preclinical data and clinical data from the IDE397 monotherapy dose escalation study of the Phase 1 clinical trial, including safety and tolerability data, pharmacokinetic data and pharmacodynamic modulation of SAM and tumor SDMA.

If GSK exercises its option and makes the related payment to us of fifty million dollars ($50,000,000), GSK would lead later-stage global clinical development.

For future development costs we will be responsible for 20% and GSK will be responsible for 80%.

Assuming GSK decides to exercise the option, we will be eligible to receive future development and regulatory milestones of up to $465 million, 50% of U.S.

net profits and tiered royalties on global non-U.S.

net sales ranging from high single digit to sub-teen double digit percentages, as well as certain commercial milestones of up to $475 million.

Our evaluation of IDE397 as a clinical candidate is supported by preclinical data.

We have evaluated the efficacy of IDE397 as monotherapy in over forty solid tumor patient derived xenograft, or PDX, models with homozygous MTAP deletions.

Results of this IDE397 MTAP-deletion PDX Panel Study were reported at AACR 2021 and show ed in vivo efficacy in multiple MTAP-null xenograft models demonstrating tumor growth inhibition when MAT2A was pharmacologically inhibited with IDE397 as monotherapy.

Results of this IDE397 MTAP-deletion PDX panel study were reported at AACR 2021 and showed in vivo efficacy in multiple MTAP-null xenograft models demonstrating tumor growth inhibition when MAT2A was pharmacologically inhibited with IDE397 as monotherapy.

In this study, we observed > 60% tumor growth inhibition, or TGI, in ~ 75% of the models and > 75% TGI in ~ 50% of models, in each case across major solid tumor types.

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Preclinical tolerability and efficacy studies are ongoing with IDE397 and various potential combination agents.

Based on preliminary results, we have observed in vivo efficacy with enhanced tumor growth inhibition for IDE397 in combination with a taxane in a pancreatic cancer PDX model and in combination with a PRMT inhibitor in an HCT116 MTAP-null cell derived xenograft, or CDX, model.

We plan to lead research and development of IDE397 through early clinical development, in collaboration with GlaxoSmithKline pursuant to the Collaboration, Option and License Agreement, or the GSK Collaboration Agreement, with an affiliate of GlaxoSmithKline, GLAXOSMITHKLINE INTELLECTUAL PROPERTY (NO.

4), Limited, or GSK.

Based on preliminary results, we have observed in vivo efficacy with enhanced tumor growth inhibition for IDE397 in combination with a taxane in a pancreatic cancer PDX model.

We are advancing our preclinical research for an inhibitor of poly (ADP-ribose) glycohydrolase, or PARG, for patients having tumors with homologous recombination deficiencies, or HRD, and potentially other genetic and/or molecular signatures.

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Small molecule inhibitors of PARG result in a dose dependent increase in cellular PAR after DNA damage.

Depletion of certain base-excision repair components sensitizes cancer cells to pharmacological PARG inhibition in vitro .

We are evaluating the efficacy of our PARG inhibitors as monotherapy across a number of solid tumor CDX and PDX models with specific genetic alterations.

One of our PARG inhibitor compounds, designated as IDB-PARG, has demonstrated dose-dependent in vivo efficacy as monotherapy with tumor regression or stasis in multiple CDX models and PDX models, including in ovarian cancer, gastric cancer and breast cancer models.

In vivo studies have shown evidence of differentiation from a PARP inhibitor, niraparib, including enhanced TGI relative to such PARP inhibitor and, in certain models, tumor regressions in models which are refractory to such PARP inhibitor.

In vivo studies in CDX and PDX models have shown evidence of differentiation from a PARP inhibitor, niraparib, including enhanced TGI relative to such PARP inhibitor and, in certain models, tumor regressions in models which are refractory to such PARP inhibitor.

We have also observed dose-dependent modulation of a PD biomarker, poly (ADP-ribose), or PAR, polymer chains across multiple in vivo CDX models, including in ovarian cancer, gastric cancer and breast cancer models.

Through our participation in the DepMap consortium, we have conducted a PRISM screen of a panel of over 800 cell lines for pharmacological sensitivity to our IDB-PARG inhibitor compound.

This PRISM screen has identified additional tumor lineages, potentially enabling additional biomarker discovery and clinical opportunity expansion for our PARG inhibitors.

In addition, we have established a strategic collaboration with the Broad Institute focused on synthetic lethality target and biomarker discovery.

We have established a strategic collaboration with the Broad Institute focused on synthetic lethality target and biomarker discovery.

Through this collaboration with the Broad Institute, we are evaluating paralog CRISPR knockdown in selected cell lines in conjunction with pharmacological inhibition of PARG to inform patient selection and combination strategies in ovarian and breast cancer.

We own or control all commercial rights in our PARG program, subject to certain economic obligations pursuant to our exclusive, worldwide license with Cancer Research UK / University of Manchester.

Subject to further preclinical studies, we are targeting to identify a PARG inhibitor development candidate in 2021.

Subject to further preclinical studies, we plan to identify a PARG inhibitor development candidate in the fourth quarter of 2021.

We are progressing our program targeting DNA Polymerase Theta, or Pol Theta or POLQ, in collaboration with GSK, for patients having solid tumors with BRCA or other homologous recombination deficiency, or HRD, mutations.

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Tumor regressions were observed for all animals in the study which were administered the combination.

Through our participation in the DepMap consortium, and in collaboration with GSK, we have conducted a PRISM screen of a panel of over 800 cell lines for pharmacological sensitivity to one of our Pol Theta ATPase inhibitor compounds.

This PRISM screen has identified additional tumor lineages, potentially enabling additional biomarker discovery and clinical opportunity expansion for our Pol Theta inhibitors.

We plan to continue further development of our POLQ program, including both protein degraders and small molecule inhibitors in collaboration with GSK pursuant to the GSK Collaboration Agreement, and are targeting selecting a development candidate for a Pol Theta small molecule inhibitor in 2021.

We plan to continue further development of our POLQ program, including both protein degraders and small molecule inhibitors , in collaboration with GSK pursuant to the GSK Collaboration Agreement, and are planning to select a development candidate for a Pol Theta small molecule inhibitor in the fourth quarter of 2021.

Werner Helicase

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Other Synthetic Lethality Pipeline Programs

We have initiated early preclinical research programs to identify small molecule inhibitors for an MTAP-synthetic lethality, or MTAP-SL, target, as well as for multiple distinct DNA Damage Targets, or DDTs, for patients with solid tumors characterized by a proprietary biomarker or a gene signature.

We have initiated early preclinical research programs to identify small molecule inhibitors for a target in the MTAP-synthetic lethality pathway, or MTAP-SL.

We believe an MTAP-SL inhibitor may be complementary to our IDE397 clinical candidate targeting MAT2A.

We have also initiated early preclinical research programs targeting multiple distinct DNA Damage Targets, or DDTs, for patients with solid tumors characterized by proprietary biomarkers or gene signatures.

We own or control all commercial rights in our MTAP-SL and DDT programs.

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We have established a comprehensive platform to computationally and empirically identify high value synthetic lethal pairs in defined patient populations.

This platform integrates information across parallel data sets, each including orthogonal content based on particular screening efforts.

This platform integrates information across parallel data sets, each including orthogonal content based on particular screening approaches.

These screens include evaluation of curated, genetically defined and preselected model cell sets indicative of targeted patient populations.

Our platform includes a proprietary library and data set resulting from our DECIPHER™ Dual CRISPR Synthetic Lethality library constructed in collaboration with University of California, San Diego.

The platform includes data from our proprietary Paralogous Gene Evaluation in Ovarian cancer, or PAGEO™, library being developed in collaboration with the Broad Institute utilizing the Sellers laboratory CRISPR paralog screening platform to evaluate functionally redundant paralogous genes across ovarian cancer subtypes.

The platform includes data from our proprietary Paralogous Gene Evaluation in Ovarian cancer, or PAGEO™, library being developed in collaboration

with the Broad Institute utilizing the Sellers L aboratory CRISPR paralog screening platform to evaluate functionally redundant paralogous genes across ovarian cancer subtypes.

Additionally, we are members of the DepMap consortium through which we have access to a comprehensive data set of genome-wide cell-based screens, including isogenic screens, conducted by the Broad Institute and other contributing institutes, including pre-publication access to new data releases.

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PKC is a protein kinase that functions downstream of the GTPases GNAQ and GNA11.

We initiated a Phase 1/2 clinical trial IDE196-001 in June 2019 to evaluate darovasertib in solid tumors harboring GNAQ or GNA11 hotspot mutations in a basket trial design, including in metastatic uveal melanoma, or MUM, and other solid tumor indications such as skin (cutaneous) melanoma.

Our clinical trial strategy in MUM includes darovasertib combination therapies, including with binimetinib, a MEK inhibitor, and independently with crizotinib, a cMET inhibitor.

We are continuing to enroll MUM patients into each of these combination arms of the Phase 1/2 clinical trial.

We anticipate providing a clinical data update for the darovasertib combination(s) in the second half of 2021.

We are evaluating darovasertib in combination with binimetinib and crizotinib pursuant to our Clinical Trial Collaboration and Supply Agreement, or Pfizer Agreement, with Pfizer, Inc.

We are clinically evaluating darovasertib in a Phase 1/2 clinical trial, designated as IDE196-001 in solid tumors harboring GNAQ or GNA11 hotspot mutations in a basket trial design, including in metastatic uveal melanoma, or MUM, and other solid tumor indications such as skin (cutaneous) melanoma.

Our clinical trial strategy in MUM includes darovasertib monotherapy as well as darovasertib combination therapies, including with binimetinib, a MEK inhibitor, and independently with crizotinib, a cMET inhibitor .

As of June 22, 2021, we have enrolled 30 MUM patients into the darovasertib/binimetinib combination arm, and 15 MUM patients into the darovasertib /crizotinib combination arm, and we are continuing patient enrollment in the dose expansion cohort of each of these combination arms .

We are expecting a clinical data update for the darovasertib combination(s) in the fourth quarter of 2021.

We are evaluating darovasertib in combination with binimetinib, and independently, with crizotinib pursuant to our Clinical Trial Collaboration and Supply Agreement, or Pfizer Agreement, with Pfizer, Inc.

We and Pfizer have formed a joint development committee responsible for coordinating all regulatory and other activities under the Pfizer Agreement, including for both the darovasertib / binimetinib combination arm and the darovasertib / crizotinib combination arm of the clinical trial.

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Darovasertib / Binimetinib Combination Therapy

In June 2020, we initiated a combination arm of our Phase 1/2 clinical trial to evaluate darovasertib in combination with binimetinib in patients having tumors harboring activating GNAQ or GNA11 hotspot mutations.

A combination arm of our Phase 1/2 clinical trial is evaluating darovasertib in combination with binimetinib in patients having tumors harboring activating GNAQ or GNA11 hotspot mutations.

An ongoing dose expansion portion of this arm of the clinical trial is evaluating the safety and efficacy of darovasertib in combination with binimetinib in patients with MUM.

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As of April 13, 2021, 24 MUM patients have enrolled in the darovasertib and binimetinib combination study and 14 of these patients were evaluable, including eight patients dosed in the Phase 1/2 dose expansion cohort of the combination study.

As of April 13, 2021 data and analyses cutoff, based on preliminary data from an unlocked database, we observed two partial responses, or PRs, including one confirmed PR and one unconfirmed PR, out of nine evaluable MUM patients with at least two post-baseline scans (22%) pursuant to RECIST 1.1 guidelines.

As of April 13, 2021 data and analyses cutoff, based on preliminary data from an unlocked database, we observed two partial responses, or PRs, including one confirmed PR and one unconfirmed PR with a 40.5% tumor reduction, which was subsequently confirmed with a 51.7% tumor reduction after the next scan following the data cut-off date.

This reflects two confirmed PR out of nine evaluable MUM patients with at least two post-baseline scans (22%) per RECIST 1.1 guidelines.

We also observed tumor reduction in 11 patients, reflecting seventy-nine percent (79%) of 14 evaluable MUM patients with at least one post-baseline scan.

Drug-related adverse events observed in the darovasertib and binimetinib combination arm in MUM as of April 13, 2021, based on preliminary data from an unlocked database, primarily include:

serious adverse events for liver toxicity, nausea and vomiting, and syncope;

and adverse events that occurred in greater than 10% of patients of nausea, vomiting, diarrhea, rash, edema, aminotransaminase, or AST increase, alanine aminotransferase, or ALT, increase and creatine phosphokinase, or CK, increase.

Drug-related adverse events observed in the darovasertib/binimetinib combination arm in MUM as related to darovasertib as of June 22, 2021 primarily include:

serious adverse events of liver toxicity, nausea and vomiting, syncope and fall;

and adverse events, that occurred in greater than 10% of patients, of nausea, vomiting, diarrhea, rash, edema, aminotransminase, or AST, increase, alanine aminotransferase, or ALT, increase, fatigue, hypotension and creatine phosphokinase, or CK, increase.

We are continuing patient enrollment into the darovasertib / binimetinib combination Phase 1/2 expansion arm under the Pfizer Agreement.

We and Pfizer amended the Pfizer Agreement in April 2021 to support a target enrollment of approximately 40 patients in the darovasertib and binimetinib clinical combination arm of the Phase 1/2 clinical trial evaluating darovasertib in MUM.

We and Pfizer amended the Pfizer Agreement in April 2021 to support a target enrollment of approximately 40 patients in the darovasertib and binimetinib clinical combination arm in MUM.

Darovasertib / Crizotinib Combination Therapy

In September 2020, we expanded the scope of our Pfizer Agreement to evaluate darovasertib and crizotinib as a combination therapy in patients having tumors harboring activating GNAQ or GNA11 hotspot mutations.

In December 2020, we initiated a combination arm of our Phase 1/2 clinical trial to evaluate darovasertib in combination with crizotinib in patients having tumors harboring activating GNAQ or GNA11 hotspot mutations.

An initial dose escalation portion of this arm of the clinical trial is evaluating the safety and efficacy of darovasertib in combination with crizotinib at various dose combinations, initially in patients with MUM.

We are also evaluating darovasertib and crizotinib as a combination therapy in patients having tumors harboring activating GNAQ or GNA11 hotspot mutations.

An ongoing dose expansion portion of this arm of the clinical trial is evaluating the safety and efficacy of darovasertib in combination with crizotinib in patients with MUM.

Following our evaluation of tolerability and preliminary efficacy from the darovasertib / crizotinib combination arm of the clinical trial in MUM, we may also evaluate darovasertib / crizotinib combination therapy in patients having other solid tumors with activating GNAQ/11 hotspot mutations outside of uveal melanoma, such as skin melanoma.

As of May 5, 2021, 6 MUM patients have enrolled in the darovasertib and crizotinib combination study and 2 of these patients were evaluable for response with one post-baseline scan.

As of data and analyses cutoff on May 5, 2021 and based on preliminary data from an unlocked database, we observed early clinical efficacy of the darovasertib and crizotinib combination in MUM with tumor reduction in 2 of 2 evaluable patients in a first cohort, including one unconfirmed partial response in a 3rd-line patient with a 54% tumor reduction, which is the deepest response, as reflected by the largest percentage reduction in tumor size, reported in the darovasertib clinical trial to date;

this patient is awaiting a confirmatory scan.

Drug-related adverse events observed in the darovasertib and crizotinib combination arm in MUM as of May 5, 2021, based on preliminary data from an unlocked database, primarily include:

serious adverse events of syncope and hypotension, each of which resolved with continued dosing;

and adverse events that occurred in at least two of the six treated patients of nausea, diarrhea, vomiting, edema, decreased appetite, and syncope.

We have initiated dose expansion for a cohort of the darovasertib / crizotinib combination arm and are continuing patient enrollment into the Phase 1/2 darovasertib / crizotinib combination arm.

As of data and analyses cutoff on May 5, 2021 and based on preliminary data from an unlocked database, we observed early clinical efficacy of the darovasertib and crizotinib combination in MUM with tumor reduction in 2 of 2 evaluable patients in a first cohort, including one unconfirmed partial response in a 3rd-line patient with a 54% tumor reduction, which was subsequently confirmed with a 56.5% tumor reduction after the next scan following the data cut-off date.

This represents the deepest response observed in the Phase 1/2 clinical trial evaluating darovasertib as monotherapy or in combinations, as reflected by the largest percentage reduction in tumor size.

Drug-related adverse events observed in the darovasertib/crizotinib combination arm in MUM as of June 22, 2021, based on preliminary data from an unlocked database, primarily include:

serious adverse events of syncope and hypotension, each of which resolved with patients continuing dosing;

and adverse events that occurred in at least two of the treated patients include nausea, diarrhea, vomiting, edema, decreased appetite, rash, hypotension and syncope.

The observed syncope and hypotension were transient, often occurring in the first week of dosing, and are being managed and mitigated through a one week run-in dosing regimen and by limiting use of certain concurrent medications, such as diuretics.

In June 2021, we initiated the dose expansion cohort of the darovasertib/crizotinib combination arm in MUM based on the observed early clinical activity of this combination.

We are continuing patient enrollment into the Phase 1/2 darovasertib/crizotinib combination arm under the Pfizer Agreement.

We and Pfizer amended the Pfizer Agreement in August 2021 to support a n additional 40 patients in the Phase 1 study in MUM .

We identified cMET as a potential biomarker and a cMET inhibitor as potential combination agent though our translational research studies, or IDE196 cMET Translational Studies.

In these studies, we observed preclinical synergies between darovasertib and crizotinib in relevant cellular models under conditions simulating a tumor microenvironment in the liver, the site of approximately 90% of uveal melanoma metastases.

Additionally, we conducted a retrospective analysis of human clinical samples from the Novartis darovasertib Phase 1 clinical trial, which correlated cMET express and activation to clinical response, and independently supported cMET expression /

activation as potential biomarker / combination agent.

We presented data summarizing the preclinical synergy results of the IDE196 cMET Translational Studies at AACR 2021.

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Regulatory Strategy

We are targeting FDA guidance in the second half of 2021 for evaluating darovasertib in a potential registrational study in patients with MUM.

randomized design and OS endpoint in first line (1L) or second, third line or later lines (2L/3L+) of therapy MUM patients.

We are planning to seek FDA regulatory guidance for darovasertib monotherapy based on observed overall survival data in MUM in the second half of 2021, and/or for darovasertib combination(s) on potential registration-enabling trial design in MUM in the first half of 2022.

We believe that the darovasertib monotherapy BID MUM data observed as of the April 13, 2021 data and analyses cutoff, and based on preliminary data from an unlocked database, supports a potential registrational study with a randomized design and OS endpoint in first line (1L) or second, third line or later lines (2L/3L+) of therapy MUM patients.

We also believe that the preliminary data for the darovasertib / binimetinib combination therapy reported as of the April 13, 2021 data and analyses cutoff, and based on preliminary data from an unlocked database, subject to the data maturing with similar or improved efficacy and acceptable tolerability, may support a potential registrational study with a single arm design and an overall response rate, or ORR, endpoint in 1L or in 2L/3L+ MUM patients, and potentially with an accelerated approval pathway.

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We plan to evaluate clinical tolerability and efficacy data from each of the ongoing darovasertib monotherapy Phase 1 portion of the clinical trial in MUM patients and the darovasertib combination therapy Phase 1/2 portions of the clinical trial in MUM patients, as well as potential strategic partnering of the darovasertib program, prior to initiation of a potentially registrational clinical trial in MUM.

We will provide updated guidance on timing for a potential NDA submission for darovasertib in MUM after making such decision on a potential registrational pathway in MUM.

Other Potential Indications

We are continuing our preclinical evaluation and are evaluating the potential for clinical evaluation of darovasertib in Sturge-Weber Syndrome, or SWS, a rare neurocutaneous disorder characterized by capillary malformations and associated with mutations in GNAQ.

Our preclinical evaluation will include potential feasibility for pediatric use.

We are continuing our preclinical evaluation and are evaluating the potential for clinical evaluation of darovasertib in GNAQ mutation-mediated rare diseases, including in Sturge-Weber Syndrome, or SWS, and Port Wine Stains, or PWS, neurocutaneous disorders characterized by capillary malformations and associated with mutations in GNAQ.

We are targeting FDA clearance in the first half of 2022 to initiate a Phase 1 clinical trial to evaluate darovasertib in SWS and, subject to further preclinical and clinical data, potentially also in PWS patients with extensive involvement.

SWS is associated with a somatic, activating hotspot mutation in GNAQ through which PKC may mediate disease pathology, as reported by Shirley et al., NEJM (2013).

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It is understood to affect the skin in the distribution of the ophthalmic branch of the trigeminal nerve and is associated with venous-capillary abnormalities of the leptomeninges.

In January 2020, we entered into a Sponsored Research Agreement with Boston Children’s Hospital for preclinical evaluation of the role of PKC in SWS.

The US/EU5 prevalence of SWS patients who may potentially benefit from long term chronic treatment is approximately 13,000 to 33,000 patients.

PWS is a potential related indication with an estimated US/EU5 prevalence of patients with extensive involvement – who have port-wine-stain over the trunk and extremities as well as the head and neck, of approximately 235,000 patients.

We entered into a Sponsored Research Agreement with Boston Children’s Hospital for preclinical evaluation of the role of PKC in SWS.

Under the agreement, we are collaborating with and support research at Boston Children’s Hospital in the laboratory of Dr.

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For example, patients are continuing on darovasertib therapy, which is an oral drug and is being shipped to and self-administered by patients at home.

Patients are being monitored through a combination of telemedicine visits

and local visits.

Patients are being monitored through a combination of telemedicine visits and local visits.

COVID‐19 infection rates have fluctuated over the course of the pandemic in several states in which our clinical trial sites are located.

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We plan to continue to use third-party service providers, including clinical research organizations, or CROs, and clinical manufacturing organizations, or CMOs, to carry out our preclinical and clinical development and manufacture and supply of our preclinical and clinical materials to be used during the development of our product candidates.

Certain of our CROs have clinical trial support personnel, including related to data management and master file management, based in India which has experienced a recent surge in COVID-19 infections.

Certain of our CROs have clinical trial support personnel, including personnel related to our data management and master file management, that are based in India which has experienced a recent surge in COVID-19 infections.

To date, the COVID-19 pandemic has not materially affected our supply chain or development schedule, but further escalation of the health crisis has the potential to cause delays in our supply chain, manufacturing operations and trial support services, which could materially adversely impact our business.

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During the three months ended March 31, 2021, we sold an aggregate of 2,712,654 shares of our common stock for net proceeds of $41.9 million at a weighted average sales price of approximately $15.98 per share under an at-the-market offering pursuant to the August 2020 and January 2021 Sales Agreements with Jefferies as sales agent.

Subsequent to March 31, 2021, from April 1, 2021 through May 9, 2021, we sold an additional 633,304 shares of our common stock for aggregate gross proceeds of $14.6 million at a weighted average sales price of approximately $22.99 per share under an at-the-market offering pursuant to the January 2021 Sales Agreements with Jefferies as sales agent.

During the three months ended June 30, 2021, we sold an aggregate of 695,218 shares of our common stock for net proceeds of $15.4 million at a weighted average sales price of approximately $22.95 per share under an at-the-market offering pursuant to the January 2021 Sales Agreements with Jefferies as sales agent.

Public Offering and Sale of IDEAYA Common Stock

On July 12, 2021, we closed on an underwritten public offering, or the Offering, of 5,333,333 shares of our common stock at an offering price of $17.25 per share, including 695,652 shares of common stock upon the exercise in full of the overallotment option by the underwriters, pursuant to which we received aggregate net proceeds of $86.5 million, after deducting underwriting discounts and commissions but before deducting other offering expenses.

Corporate Update

We do not have any products approved for sale and have not generated any revenue since inception.

We have funded our operations through March 31, 2021 primarily through the sale and issuance of common stock, redeemable convertible preferred stock, and convertible promissory notes, including our initial public offering, or IPO, in May 2019, a follow-on public offering in June 2020, a direct private placement equity investment by Glaxo Group Limited, or GGL, an affiliate of GlaxoSmithKline, in June 2020, and through the sale and issuance of common stock under our at-the-market facility pursuant to the August 2020 and January 2021 Sales Agreements

with Jefferies as sales agent.

In July 2020, we received a non-dilutive upfront cash payment from GSK in connection with the GSK Collaboration Agreement .

We have funded our operations through June 30, 2021 primarily through the sale and issuance of common stock, redeemable convertible preferred stock, and convertible promissory notes, including our initial public offering, or IPO, in May 2019, a follow-on underwritten public offering in June 2020, a direct private placement equity investment by Glaxo Group Limited, or GGL, an affiliate of GlaxoSmithKline, in June 2020, the sale and issuance of common stock under our at-the-market facility pursuant to the August 2020 and January 2021 Sales Agreements with Jefferies as sales agent, and through a follow-on underwritten public offering in July 2021.

Additionally, we received a non-dilutive upfront cash payment from GSK in July 2020 in connection with the GSK Collaboration Agreement.

Since our inception in June 2015, we have devoted substantially all of our resources to discovering and developing our product candidates.

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In addition, we expect to incur additional costs associated with operating as a public company.

Our net losses were $9.0 million and $12.0 million for the three months ended March 31, 2021 and March 31, 2020, respectively.

As of March 31, 2021, we had an accumulated deficit of $136.0 million.

Our net losses were $20.0 million and $24.4 million for the six months ended June 30, 2021 and June 30, 2020, respectively.

As of June 30, 2021, we had an accumulated deficit of $147.0 million.

Our ability to generate product revenue will depend on the successful development, regulatory approval and eventual commercialization of one or more of our product candidates, ourselves, or for some programs, in collaboration with our strategic partners.

We are leading and solely responsible for preclinical, translational and clinical research and development, as applicable, for (i) the darovasertib monotherapy arm of our IDE196-001 clinical trial, (ii) our PARG program and (iii) our earlier pipeline programs, including our DNA Damage Target or DDT programs and our MTAP-SL program.

We are leading and solely responsible for preclinical, translational and clinical research and development, as applicable, for (i) the darovasertib monotherapy arm of our IDE196-001 clinical trial, (ii) our PARG program and (iii) our earlier pipeline programs, including our MTAP-SL program and our DNA Damage Target or DDT programs.

We are leading clinical development in the ongoing darovasertib / binimetinib combination arm and the ongoing darovasertib /crizotinib combination arm of our IDE196-001 clinical trial, in each case in coordination with Pfizer pursuant to the Pfizer Agreement.

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If we fail to raise capital or enter into such agreements as and when needed, we may have to significantly delay, scale back or discontinue the development and commercialization of our product candidates.

As of March 31, 2021, we had cash, cash equivalents, and short-term and long-term marketable securities of $310.4 million.

As of June 30, 2021, we had cash, cash equivalents, and short-term and long-term marketable securities of $312.4 million.

We believe that our cash, cash equivalents, and short-term and long-term marketable securities will be sufficient to fund our planned operations for at least 12 months from the date of the issuance of these financial statements.

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Substantially all of our research and development expenses consist of expenses incurred in connection with discovery and development of our product candidates.

These expenses include certain payroll and personnel-related expenses, including salaries, employee benefit costs and stock-based compensation expenses for our research and product development employees, fees to third parties to conduct certain research and development activities on our behalf including fees to CMOs and CROs in support of manufacturing and clinical activity for darovasertib (IDE196), consulting costs, costs for laboratory supplies, costs for product licenses and allocated overhead, including rent, equipment, depreciation, information technology costs and utilities.

These expenses include certain payroll and personnel-related expenses, including salaries, employee benefit costs and stock-based compensation expenses for our research and product development employees, fees to third parties to conduct certain research and development activities on our behalf including fees to CMOs and CROs in support of manufacturing and clinical activity for IDE397 and darovasertib (IDE196), consulting costs, costs for laboratory supplies, costs for product licenses and allocated overhead, including rent, equipment, depreciation, information technology costs and utilities.

We expense both internal and external research and development expenses as they are incurred.

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With respect to internal costs, several of our departments support multiple product candidate research and development programs, and therefore the costs cannot be allocated to a particular product candidate or development program.

The following table summarizes our external clinical development expenses by program for the three months ended March 31, 2021 and December 31, 2020:

The following table summarizes our external clinical development expenses by program for the three months ended June 30, 2021 and March 31, 2021:

Three Months Ended

June 30, 2021

March 31, 2021

December 31, 2020

External clinical development expenses (1) :

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These expenses are primarily for services provided by external consultants, CMOs and CROs.

The following table summarizes our external clinical development expenses by program for the three months ended March 31, 2021 and March 31, 2020:

Three Months Ended March 31,

The following table summarizes our external clinical development expenses by program for the six months ended June 30, 2021 and June 30, 2020:

Six Months Ended

June 30, 2021

June 30, 2020

External clinical development expenses (1) :

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Results of Operations

Pursuant to Item 303(c)(2)(ii) of Regulation S-K, amended by Release No.

33-10890, we have elected to discuss any material changes in our results of operations, by comparing our most recently completed quarter to the immediately preceding quarter.

We believe the comparison of the most recently completed quarter to the immediately preceding quarter provides more relevant information for our investors to analyze our business activities.

We also continue to discuss any material changes in our results of operations for the most recent fiscal year-to-date period, compared to the corresponding year-to-date period of the preceding fiscal year, pursuant to Item 303(c)(2)(i) of Regulation S-K.

Comparison of Three Months Ended March 31, 2021 and December 31, 2020

Comparison of Three Months Ended June 30, 2021 and March 31, 2021

The following table summarizes our results of operations for the periods indicated (in thousands):

Three Months Ended

June 30, 2021

March 31, 2021

December 31, 2020

Collaboration revenue

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Collaboration Revenue

Collaboration revenue decreased by $3.3 million, or 31%, in from the three months ended December 31, 2020 to the three months ended March 31, 2021.

Collaboration revenue increased by $ 1.5 million, or 21%, in from the three months ended March 31, 2021 to the three months ended June 30, 2021.

In July 2020, the GSK Collaboration Agreement became effective, and we started recognizing collaboration revenue, which consists of revenue from preclinical and Phase 1 monotherapy clinical research and development services under the MAT2A program as well as preclinical research services and the related license under the Pol Theta and WRN programs.

Revenue we recognize from satisfaction of performance obligations under the GSK Collaboration Agreement is impacted by our estimates of the remaining cots to complete our obligations, which require significant judgment, and may cause fluctuation in the revenue recognized from period to period.

The fluctuation from the three months ended December 31, 2020 to the three months ended March 31, 2021 is due to timing of services performed.

Revenue we recognize from satisfaction of performance obligations under the GSK Collaboration Agreement is impacted by our estimates of the remaining costs to complete our obligations, which require significant judgment, and may cause fluctuation in the revenue recognized from period to period.

The fluctuation from the three months ended March 31, 2021 to the three months ended June 30, 2021 is due to timing of services performed.

Research and Development Expenses

Research and development expenses decreased by $0.5 million, or 4%, from the three months ended December 31, 2020 to the three months ended March 31, 2021.

The decrease in research and development expenses was primarily due to a decrease in fees paid to CROs, CMOs and consultants of $1.3 million related to the advancement of our lead product candidates through preclinical studies, a decrease in external clinical development expenses for IDE397 of $0.5 million related to manufacturing and clinical startup activities for our Phase 1 clinical trial, a decrease in external clinical development expenses for darovasertib of $0.1 million related to support costs for our Phase 1/2 clinical trial to evaluate darovasertib in solid tumors, partially offset by an increase in payroll expenses, including salaries, benefits and stock-based compensation expense of $1.2 million related to an increase in headcount to support our growth, and an increase in costs for laboratory supplies used in support of our research programs of $0.2 million.

Research and development expenses increased by $3.4 million, or 30%, from the three months ended March 31, 2021 to the three months ended June 30, 2021.

The increase in research and development expenses was primarily due to an increase in fees paid to CROs, CMOs and consultants of $2.5 million related to the advancement of our lead product candidates through preclinical studies, an increase in payroll expenses, including salaries, benefits and stock-based compensation expense of $0.6 million related to an increase in headcount to support our growth, an increase in external clinical development expenses for darovasertib of $0.3 million related to support costs for our Phase 1/2 clinical trial to evaluate darovasertib in solid tumors, and an increase in costs for laboratory supplies used in support of our research programs of $0.2 million, partially offset by a decrease in external clinical development expenses for IDE397 of $0.2 million related to manufacturing and method validation activities for our Phase 1 clinical trial.

General and Administrative Expenses

General and administrative expenses increased by $1.0 million, or 27%, from the three months ended December 31, 2020 to the three months ended March 31, 2021.

The increase in general and administrative expenses was primarily due to an increase in payroll expenses, including salaries, benefits and stock-based compensation expense, of $0.6 million related to increased headcount to support our growth as a public company, an increase in costs associated with the filing of a shelf registration statement on Form S-3 of $0.1 million, and an increase in legal patent expense of $0.1 million due to increased patent filings.

General and administrative expenses were in line from the three months ended March 31, 2021 to the three months ended June 30, 2021.

Increase in general and administrative expenses due to an increase in payroll expenses, including salaries, benefits and stock-based compensation expense of $0.1 million related to increased headcount to support our growth as a public company were offset by a decrease in audit fees for the comparative periods.

Interest Income and Other Income (Expense), Net

Interest income and other income (expense), net decreased by $31,000, or 21%, from the three months ended December 31, 2020 to the three months ended March 31, 2021, primarily due to a decrease in interest income on our cash, cash equivalents, and short-term and long-term marketable securities balances, as a result of the lower interest rate yields.

Comparison of Three Months Ended March 31, 2021 and 2020

Interest income and other income (expense), net decreased by $10,000, or 9%, from the three months ended March 31, 2021 to the three months ended June 30, 2021, primarily due to a decrease in interest income on our cash, cash equivalents, and short-term and long-term marketable securities balances, as a result of the lower interest rate yields.

Comparison of Six Months Ended June 30, 2021 and 2020

The following table summarizes our results of operations for the periods indicated (in thousands):

Three Months Ended March 31,

Six Months Ended June 30,

Collaboration revenue

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Collaboration Revenue

Collaboration revenue increased by $7.2 million in the three months ended March 31, 2021.

Collaboration revenue increased by $16.0 million in the six months ended June 30, 2021.

In July 2020, the GSK Collaboration Agreement became effective, and we started recognizing collaboration revenue.

We recognized revenue from preclinical and Phase 1 monotherapy clinical research and development services under the MAT2A program as well as preclinical research services and the related license under the Pol Theta and WRN programs in the three months ended March 31, 2021.

Research and Development Expenses

Research and development expenses increased by $2.5 million, or 28%, from the three months ended March 31, 2020 to the three months ended March 31, 2021.

The increase in research and development expenses was primarily due to an increase in payroll expenses, including salaries, benefits and stock-based compensation expense, of $1.3 million related to an increase in headcount to support our growth, an increase in external clinical development expenses for IDE397 of $1.0 million related to related to manufacturing and clinical startup activities for our Phase 1 clinical trial, an increase in fees paid to CROs, CMOs and consultants of $0.2 million related to the advancement of our lead product candidates through preclinical studies, an increase in costs for laboratory supplies used in support of our research programs of $0.2 million, partially offset by a decrease in external clinical development expenses for darovasertib of $0.2 million related to increased patient enrollment in our Phase 1/2 clinical trial to evaluate darovasertib in solid tumors.

Research and development expenses increased by $8.9 million, or 51%, from the six months ended June 30, 2020 to the six months ended June 30, 2021.

The increase in research and development expenses was primarily due to an increase in payroll expenses, including salaries, benefits and stock-based compensation expense, of $3.6 million related to an increase in headcount to support our growth, an increase in fees paid to CROs, CMOs and consultants of $2.5 million related to the advancement of our lead product candidates through preclinical studies, an increase in external clinical development expenses for IDE397 of $1.6 million related to manufacturing and clinical startup activities for our Phase 1 clinical trial, and an increase in costs for laboratory supplies, facilities and software to support our research programs of $1.6 million, partially offset by a decrease in external clinical development expenses for darovasertib of $0.3 million related to a decrease in manufacturing and clinical startup activities.

General and Administrative Expenses

General and administrative expenses increased by $1.4 million, or 40%, from the three months ended March 31, 2020 to the three months ended March 31, 2021.

The increase in general and administrative expenses was primarily due to an increase in payroll expenses, including salaries, benefits and stock-based compensation expense, of $1.0 million related to increased headcount to support our growth as a public company, an increase in directors’ and officers’ liability insurance premiums of $0.1 million, an increase in costs associated with the filing of a shelf registration statement on Form S-3 of $0.1 million, and an increase in software licenses of $0.1 million

General and administrative expenses increased by $2.2 million, or 30%, from the six months ended June 30, 2020 to the six months ended June 30, 2021.

The increase in general and administrative expenses was primarily due to an increase in payroll expenses, including salaries, benefits and stock-based compensation expense, of $2.0 million related to increased headcount to support our growth as a public company, an increase in software licenses and facilities expenses of $0.4 million, and an increase in directors’ and officers’ liability insurance premiums of $0.2 million, partially offset by a decrease in legal costs of $0.3 million related to the GSK Collaboration Agreement, and a decrease in costs associated with the filing of a shelf registration statement on Form S-3 of $0.2 million.

Interest Income and Other Income (Expense), Net

Interest income and other income (expense), net decreased by $0.3 million, or 74%, from the three months ended March 31, 2020 to the three months ended March 31, 2021, primarily due to a decrease in interest income on our cash, cash equivalents, and short-term and long-term marketable securities balances, as a result of the lower interest rate yields.

Interest income and other income (expense), net decreased by $0.4 million, or 66%, from the six months ended June 30, 2020 to the six months ended June 30, 2021, primarily due to a decrease in interest income on our cash, cash equivalents, and short-term and long-term marketable securities balances, as a result of the lower interest rate yields.

Liquidity and Capital Resources ;

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We have funded our operations primarily through the sale and issuance of common stock, redeemable convertible preferred stock, and convertible promissory notes, as well as the up-front payment received from GSK.

As of March 31, 2021, we had cash, cash equivalents and marketable securities of $310.4 million, consisting primarily of money market funds, U.S.

As of June 30, 2021, we had cash, cash equivalents and marketable securities of $312.4 million, consisting primarily of money market funds, U.S.

government securities, commercial paper, and corporate bonds.

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We have incurred net losses since our inception.

For the three months ended March 31, 2021 and March 31, 2020, we had net losses of $9.0 million and $12.0 million, respectively, and we expect to incur substantial additional losses in future periods.

As of March 31, 2021, we had an accumulated deficit of $136.0 million.

Based on our current business plan, we believe that our existing cash, cash equivalents and marketable securities will be sufficient to fund our planned operations into 2025.

For the six months ended June 30, 2021 and June 30, 2020, we had net losses of $20.0 million and $24.4 million, respectively, and we expect to incur substantial additional losses in future periods.

As of June 30, 2021, we had an accumulated deficit of $147.0 million.

Based on our current business plan, we believe that our existing cash, cash equivalents and marketable securities will be sufficient to fund our planned operations in support of our long term cash requirements.

To date, we have not generated any product revenue.

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In September 2019, we further amended our South San Francisco facility lease agreement to expand the size of the premises by adding 5,588 rentable square feet of additional space.

As of March 31, 2021, we expect to make the total lease payments of $7.1 million through July 2024.

As of June 30, 2021, we expect to make the total lease payments of $6.6 million through July 2024.

We enter into contracts in the normal course of business with third-party contract organizations for preclinical and clinical studies and testing, manufacture and supply of our preclinical and clinical materials and providing other services and products for operating purposes.

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The following table sets forth the primary sources and uses of cash, cash equivalents, and restricted cash for each of the periods presented below (in thousands):

Three Months Ended March 31,

Six Months Ended June 30,

Net cash provided by (used in):

4 unchanged sentences

Cash Flows from Operating Activities

Net cash used in operating activities was $13.7 million for the three months ended March 31, 2021.

Cash used in operating activities was primarily due to the use of funds in our operations to develop our product candidates resulting in a net loss of $9.0 million, a decrease in contract liabilities of $6.2 million due to revenue recognized during three months ended March 31, 2021, offset by the cost reimbursement that became unconditionally due as of March 31, 2021, and an increase in accounts receivable from GSK of $1.0 million due to the expected costs reimbursement for the quarter, partially offset by stock-based compensation expense of $1.9 million, and amortization of premiums on marketable securities of $0.5 million.

Net cash used in operating activities was $9.5 million for the three months ended March 31, 2020.

Cash used in operating activities was primarily due to the use of funds in our operations to develop our product candidates resulting in a net loss of $12.0 million, partially offset by depreciation and amortization expense of $0.3 million and stock-based compensation expense of $0.8 million, a decrease in prepaid expenses and other assets of $1.1 million due to the amortization of advance payments to CROs and CMOs, and prepayment for director and officer, or D&O, insurance, and an increase in accrued and other liabilities of $0.4 million mainly due to fees to third parties in support of clinical and preclinical activities.

Net cash used in operating activities was $26.7 million for the six months ended June 30, 2021.

Cash used in operating activities was primarily due to the use of funds in our operations to develop our product candidates resulting in a net loss of $20.0 million, adjusted for a decrease in contract liabilities of $13.6 million due primarily to revenue recognized during six months ended June 30, 2021, offset by the cost reimbursement that became unconditionally due as of June 30, 2021, and an increase in prepaid expenses and other assets of $1.7 million due to advance payment for our D&O insurance policy premiums , partially offset by stock-based compensation expense of $4.0 million, an increase in accounts payable and accrued and other liabilities of $2.5 million due primarily to fees to third parties in support of clinical and preclinical activities, amortization of premiums on marketable securities of $0.9 million, and depreciation expense of $0.8 million.

Net cash used in operating activities was $23.2 million for the six months ended June 30, 2020.

Cash used in operating activities was primarily due to the use of funds in our operations to develop our product candidates resulting in a net loss of $24.4 million, adjusted for an increase in prepaid expenses and other assets of $0.8 million mainly due to advance payment for our D&O insurance policy premiums, and a decrease in lease liabilities of $0.6 million due to lease amortization, partially offset by stock-based compensation expense of $1.6 million, depreciation and amortization expense of $0.7 million and a decrease in right-of-use assets of $0.5 million due to lease amortization.

Cash Flows from Investing Activities

Net cash provided by investing activities was $36.4 million for the three months ended March 31, 2021, which consisted of $76.2 million provided by maturities of marketable securities, partially offset by $38.7 million used to purchase marketable securities and $1.0 million used to purchase property and equipment.

Net cash provided investing activities was $10.9 million for the three months ended March 31, 2020, which consisted of $22.2 million provided by maturities of marketable securities , partially offset by $11.3 million used to purchase marketable securities.

Net cash used in investing activities was $12.9 million for the six months ended June 30, 2021, which consisted of $133.0 million used to purchase marketable securities and $1.6 million used to purchase property and equipment, partially offset by $117.7 million provided by maturities of marketable securities and $4.0 million provided by sales of marketable securities.

Net cash provided by investing activities was $41.9 million for the six months ended June 30, 2020, which consisted of $68.2 million provided by maturities of marketable securities, partially offset by $26.2 million used to purchase marketable securities and $0.1 million used to purchase property and equipment.

Cash Flows from Financing Activities

Net cash provided by financing activities was $42.0 million for the three months ended March 31, 2021, which consisted of $41.9 million of net proceeds from ATM offering, and $0.1 million of proceeds from exercise of common stock options.

Net cash provided by financing activities was less than $0.1 million for the three months ended March 31, 2020, which consisted of proceeds from exercise of common stock options.

Net cash provided by financing activities was $58.0 million for the six months ended June 30, 2021, which consisted of $57.3 million of net proceeds from ATM offering, $0.3 million of proceeds from exercise of common stock options, and $0.3 million of proceeds from ESPP purchase.

Net cash provided by financing activities was $94.7 million for the six months ended June 30, 2020, which consisted of $93.9 million of net proceeds from our follow-on offering, $0.7 million of proceeds from exercise of common stock options, and $0.1 million of proceeds from ESPP purchase.

Critical Accounting Policies

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For more detail on our critical accounting policies, refer to Note 2 to the unaudited interim condensed financial statements appearing elsewhere in this Quarterly Report on Form 10-Q, and the notes to the financial statements appearing elsewhere in our Annual Report on Form 10-K filed with the SEC on March 23, 2021.

During the three months ended March 31, 2021, except as described in Note 2 to the unaudited interim condensed financial statements appearing elsewhere in this Quarterly Report on Form 10-Q, there were no material changes to our critical accounting policies from those discussed in our Annual Report on Form 10-K filed with the SEC on March 23, 2021.

Quantitative and Qualitati ve Disclosures About Market Risk.

Interest Rate Sensitivity

The market risk inherent in our financial instruments and in our financial position represents the potential loss arising from adverse changes in interest rates or exchange rates.

As of March 31, 2021, we had cash equivalents and marketable securities of $310.1 million, consisting of interest-bearing money market funds, investments in U.S.

government securities, commercial paper, and corporate bonds, for which the fair value would be affected by changes in the general level of U.S.

interest rates.

However, due to the short-term maturities and the low-risk profile of our cash equivalents and marketable securities, an immediate 10% change in interest rates would not have a material effect on the fair value of our cash equivalents and marketable securities.

We do not believe that inflation, interest rate changes or exchange rate fluctuations have had a significant impact on our results of operations for any periods presented herein.

During the three and six months ended June 30, 2021, except as described in Note 2 to the unaudited interim condensed financial statements appearing elsewhere in this Quarterly Report on Form 10-Q, there were no material changes to our critical accounting policies from those discussed in our Annual Report on Form 10-K filed with the SEC on March 23, 2021.

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-Q

Item 2. Management’s Discussion and Analysis