SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Chk1, a
      key regulator of cell cycle progression and the DNA Damage Response (DDR) replication stress
      response. In cancer cells, intrinsic replication stress (RS) is induced by factors such as
      oncogenes (e.g., CCNE1 or MYC), genetic mutations in DNA repair machinery (e.g., BRCA1 or
      FA), genetic mutations leading to a dysregulated cell cycle (e.g., TP53 or RAD50) or other
      genomic alterations. This replication stress results in persistent DNA damage and genomic
      instability leading to an increased dependency on Chk1 for survival. Targeted inhibition of
      Chk1 by SRA737 may therefore be synthetically lethal to cancer cells with elevated intrinsic
      RS.

      The critical role of Chk1 in mediating cellular responses to RS affords the opportunity to
      combine SRA737 with sub-therapeutic concentrations of the RS-inducing agent gemcitabine. Low
      concentrations of gemcitabine cause a prolonged cell cycle S-phase and induce hallmarks of RS
      without inducing overt cytotoxicity. Gemcitabine profoundly depletes DNA replication building
      blocks and targets proliferating cells by inducing RS through induction of stalled
      replication forks. In response, Chk1 has an important role in stabilizing and preserving
      replication fork complexes in the context of RS, preventing catastrophic replication fork
      collapse and double strand breaks. Extensive preclinical data, as well as clinical data,
      support the synergistic interaction between Chk1 inhibition and gemcitabine.

      The purpose of this clinical study is to: establish the safety profile, determine the MTD,
      and propose a RP2D and schedule for SRA737 in combination with low dose gemcitabine. In
      addition, the study aims to evaluate the preliminary efficacy of SRA737 in combination with
      low dose gemcitabine in prospectively-selected subjects with tumors that have predicted
      sensitivity to Chk1 inhibition.

      This clinical study consists of three phases:

        1. A Standard-Dose Triplet Combo Dose Escalation Phase 1. This phase, which has concluded,
           evaluated a triplet combination of SRA737 with standard-dose gemcitabine and cisplatin
           in subjects with solid tumors.

        2. A Low-Dose Gemcitabine Combo Dose Escalation Phase 1. Cohorts of 3 to 6 subjects are
           being given escalating doses of SRA737 on an intermittent schedule in addition to low
           dose gemcitabine until the combination MTD is reached. The dose or frequency of
           gemcitabine may also be reduced during this process and alternative dosing schedules for
           SRA737 may be considered. When the MTD or a minimum efficacious dose range has been
           achieved for SRA737, or when evidence of anti-tumor activity is observed, the
           gemcitabine dose may be escalated with corresponding decreases in the SRA737 dose as
           necessary for safety.

        3. A Low-Dose Gemcitabine Combo Cohort Expansion Phase 2. After the MTD and/or RP2D has
           been identified, the trial will explore the preliminary efficacy of SRA737 plus low dose
           gemcitabine in prospectively-selected subjects with tumors that harbor genomic
           alterations linked to increased replication stress and that are hypothesized to be more
           sensitive to Chk1 inhibition via synthetic lethality. Enrollment for expansion cohorts
           may alternatively begin prior to the completion of dose escalation and determination of
           MTD or RP2D, if there is evidence of anti-tumor activity or if the minimal plasma
           concentration of SRA737 is maintained above a threshold at which sustained Chk1
           inhibition is anticipated at 24 hours after dosing.

      This phase is targeting enrollment of genetically-selected patients into four expansion
      cohorts from specific indications that are predicted to have a high prevalence of such
      alterations, including locally advanced or metastatic:

        -  high-grade serous ovarian cancer (HGSOC),

        -  small cell lung cancer (SCLC);

        -  soft tissue sarcoma (STS); and

        -  cervical/anogenital cancer.

      To qualify for enrolment into these cohorts, the subject's tumor must have evidence of
      predicted sensitivity to Chk1 inhibition based on factors including:

        -  For subjects with HGSOC, documented somatic or germline BRCA1 and BRCA2 wild-type status
           will confer eligibility without requirement for prospective genetic profiling. If
           documented BRCA status is not available, genetic profiling may be performed
           prospectively to determine eligibility.

        -  Subjects with SCLC are eligible without requirement for prospective genetic profiling on
           the basis of very high prevalence of cancer related alterations in the tumor suppressor
           genes (eg, TP53 and RB1) in this population.

        -  For subjects with STS, and any others for whom genetic profiling is performed
           prospectively, eligibility will be determined by the sponsor's review of genetic
           abnormalities detected in genes in the following categories:

             -  Key tumor suppressor genes regulating G1 cell cycle progression/arrest such as RB1,
                TP53, etc.

             -  The DNA damage response pathway including ATM, BRCA1, BRCA2, mismatch repair
                genetic alterations and/or high microsatellite instability.

             -  Genetic indicators of replicative stress such as gain of function/amplification of
                Chk1 or ATR or other related gene.

             -  Oncogenic drivers such as MYC, CCNE1, etc.

        -  For subjects with anogenital cancer, known HPV positive status will confer eligibility
           without requirement for prospective genetic profiling. If HPV status is not known or not
           positive, genetic profiling (or HPV testing where appropriate) may be performed
           prospectively to determine eligibility. Subjects with cervical cancer or squamous cell
           carcinoma of the anus are eligible without requirement for prospective genetic profiling
           based on the very high prevalence of HPV positivity in these populations.

      Tumor genetics will be determine using Next-Generation Sequencing.