On December 12, 2022 Loxo@Lilly, the oncology unit of Eli Lilly and Company (NYSE: LLY), reported updated clinical data from the pirtobrutinib global Phase 1/2 BRUIN trial in patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), Richter transformation (RT), and Waldenström macroglobulinemia (WM) (Press release, Eli Lilly, DEC 12, 2022, View Source [SID1234625108]). Pirtobrutinib is an investigational, highly selective, reversible (non-covalent) inhibitor of Bruton’s tyrosine kinase (BTK). These data are featured in oral and poster presentations at the 2022 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

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"These data presented at ASH (Free ASH Whitepaper) build on previous results with significantly longer follow-up and continue to expand on the body of evidence supporting pirtobrutinib as a potential treatment option for patients previously treated with a covalent BTK inhibitor across a range of B-cell malignancies," said Susan O’Brien, M.D., UCI Health hematology oncologist, Chao Family Comprehensive Cancer Center and professor of hematology/oncology at University of California, Irvine. "For patients with CLL/SLL, MCL, and Waldenström macroglobulinemia who have received the standard of care regimens, including covalent BTK inhibitors, treatment options are extremely limited. For patients with Richter transformation, there are no standard treatment options. These results show that pirtobrutinib may potentially help to address multiple areas of growing unmet need."

"We continue to be very excited by the results of pirtobrutinib across B-cell malignancies," said David Hyman, M.D., chief medical officer, Loxo@Lilly. "These data from the BRUIN Phase 1/2 trial provide further evidence that pirtobrutinib’s reversible binding mechanism and pharmacology may allow for extended targeting of the BTK pathway following treatment with a covalent BTK inhibitor. We are appreciative of the investigators and patients involved in the BRUIN study who have contributed to a better understanding of the potential of this medicine."

Key Data at ASH (Free ASH Whitepaper)

The BRUIN Phase 1/2 clinical trial is evaluating pirtobrutinib monotherapy in patients previously treated for MCL, CLL/SLL, or other non-Hodgkin lymphomas (NHL). The efficacy data being presented at ASH (Free ASH Whitepaper) for MCL and CLL/SLL are based on independent review committee (IRC) assessment while the efficacy data for RT and WM are based on investigator response assessments. The safety cohort consisted of all patients with B-cell malignancies who received at least one dose of pirtobrutinib monotherapy as of the data cutoff date.

Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

The BRUIN trial includes one of the largest prospective cohorts of BTK inhibitor pre-treated CLL/SLL patients ever studied. As of the July 29, 2022 data cutoff date, 247 patients with CLL/SLL had received a prior BTK inhibitor and enrolled prior to November 5, 2021, to ensure adequate follow-up. Patients had received a median of three prior therapies (range 1-11). In this dataset, pirtobrutinib demonstrated an overall response rate (ORR) of 82% (95% CI: 76.8-86.7) and median progression-free survival (PFS) of 19.6 months (95% CI: 16.9-22.1). In patients treated with both a prior BTK and BCL2 inhibitor (n=100, median of five prior lines of therapy), the ORR was 79% (95% CI: 69.7-86.5), and median PFS was 16.8 months (95% CI: 13.2-18.7). Response rates were consistent across all subgroups analyzed regardless of mutation status, age, or previous therapies.

Mantle Cell Lymphoma (MCL)

As of the January 31, 2022 data cutoff date, the primary analysis set consisted of the first 90 patients enrolled with MCL who had received a prior BTK inhibitor. Patients had received a median of three prior lines of therapy (range 1-8). In this dataset, pirtobrutinib demonstrated an ORR of 58% (95% CI: 46.9-68.1), a median duration of response (DoR) of 21.6 months (95% CI: 7.5-NE) and a median PFS of 7.4 months (95% CI: 5.3-12.5). Response rates were consistent regardless of number of prior lines of therapy and classes of prior therapy received.

Richter Transformation (RT)

The BRUIN trial also includes one of the largest prospective RT populations ever studied. As of the July 29, 2022 data cutoff date, 75 patients with RT were response evaluable, with 68 patients having received prior treatment for RT. Among these patients, the median number of prior lines of CLL therapy was two (range 0-11) and the median number of prior lines of RT therapy was two (range 1-7). The ORR for the 75 response-evaluable patients was 52% (95% CI: 40.2-63.7), and for the 68 patients previously treated for RT, the ORR was 50% (95% CI: 37.6-62.4). Among all response evaluable patients, median overall survival (OS) was 13.1 months (95% CI: 7.8-NE) and DoR was 5.6 months (95% CI: 2.5-NE), regardless of prior RT therapy.

Waldenström Macroglobulinemia (WM)

As of the July 29, 2022 data cutoff date, 80 patients with WM were response evaluable, with 63 patients having received prior treatment with a BTK inhibitor. Among the 63 patients, the median number of prior therapies was three (range 1-11). The major response rate (MRR) was 67% (95% CI: 53.7-78.0), including 15 (23.8%) very good partial responses and 27 (42.9%) partial responses. In patients who previously received both chemoimmunotherapy and a covalent BTK inhibitor (n=50), the MRR was 68% (95% CI: 53.3-80.5). Median PFS was 19.4 months (95% CI: 15.1-22.1) in patients who received previous treatment with a covalent BTK inhibitor (n=62).

Safety of Pirtobrutinib from the BRUIN Study

In the safety cohort of all pirtobrutinib-treated patients (n=773), the most frequent treatment-emergent adverse events (TEAE) (≥15%), regardless of attribution, were fatigue (29%), diarrhea (24%), and contusion (19%). The most frequent Grade ≥3 TEAE was neutropenia (20%). Low rates of Grade ≥3 TEAEs of hypertension (9%), hemorrhage (11%), and atrial fibrillation/flutter (3%) were observed. Overall, discontinuations due to a treatment-related adverse event occurred in 3% (n=20) of all patients. The safety profile was generally consistent across the populations studied.

Safety and Tolerability in Covalent BTK Intolerant Patients

The safety and tolerability of pirtobrutinib monotherapy in patients with relapsed or refractory B-cell malignancies who were intolerant to a prior covalent BTK inhibitor (n=127) was evaluated. Atrial fibrillation was among the most common adverse events (AE) that led to the discontinuation of a prior covalent BTK inhibitor, and in these patients (n=30), this AE recurred with pirtobrutinib treatment in two patients. Most patients did not experience high-grade recurrence of the other common AEs that led to discontinuation of a prior covalent BTK inhibitor, with the exception of neutropenia (in the patients in whom neutropenia recurred, 67% were Grade ≥3). No patient who discontinued a prior BTK inhibitor due to an AE had to discontinue pirtobrutinib for the same AE.

Loxo@Lilly is studying pirtobrutinib in multiple Phase 3 studies. Details on the trials can be found at lillyloxooncologypipeline.com or by visiting clinicaltrials.gov.

About Pirtobrutinib (LOXO-305)
Pirtobrutinib is an investigational, highly selective, reversible (non-covalent) Bruton’s tyrosine kinase (BTK) inhibitor. BTK plays a key role in the B-cell antigen receptor signaling pathway, which is required for the development, activation and survival of normal white blood cells, known as B-cells, and malignant B-cells. BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenström macroglobulinemia (WM). Pirtobrutinib was developed to reversibly bind BTK, deliver consistently high target coverage regardless of BTK turnover rate, and preserve activity in the presence of the C481 acquired resistance mutations. Pirtobrutinib was found to be highly selective – 300 times more selective in BTK inhibition versus 98% of other kinases tested in preclinical studies. Interested patients and physicians can contact the Loxo@Lilly Physician and Patient BTK Clinical Trial Hotline at 1-855-LOXO-305 or email [email protected].

About the BRUIN Phase 1/2 Trial

The BRUIN Phase 1/2 clinical trial is the ongoing first-in-human, global, multi-center evaluation of pirtobrutinib in patients previously treated for mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or other non-Hodgkin lymphomas (NHL).

The trial includes a Phase 1 dose-escalation phase, a Phase 1b combination arm, and a Phase 2 dose-expansion phase. The primary endpoint of the Phase 1 study is maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D). Secondary endpoints include safety, pharmacokinetics (PK), and preliminary efficacy measured by overall response rate (ORR) for monotherapy. The primary endpoint of the Phase 1b study is safety of the drug combinations. The secondary endpoints are PK and preliminary efficacy measured by ORR for the drug combinations. The primary endpoint for the Phase 2 study is ORR as determined by an independent review committee (IRC). Secondary endpoints include ORR as determined by investigator, best overall response (BOR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), safety, and PK.

On December 12, 2022 Eagle Pharmaceuticals, Inc. (Nasdaq: EGRX) ("Eagle" or the "Company") reported that it has reached a settlement agreement with Accord Healthcare, Inc. ("Accord"). Eagle had asserted its Orange Book-listed patents against Accord related to Accord’s new drug application ("NDA") referencing BENDEKA. The settlement agreement provides that Accord has the right to market its product beginning January 17, 2028, or earlier based on certain circumstances. The settlement agreement is confidential and subject to review by the U.S. Federal Trade Commission and the U.S. Department of Justice.

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The settlement with Accord follows Eagle’s previously announced settlement with Hospira, Inc. ("Hospira") regarding two Orange Book-listed patents, which granted Hospira the right to market its product beginning January 17, 2028, or earlier based on certain circumstances.

"We are pleased with the settlement. Eagle intends to continue to expand and vigorously enforce its intellectual property rights around BENDEKA and our bendamustine franchise," stated Scott Tarriff, President and Chief Executive Officer of Eagle.

On December 12, 2022 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported positive updated clinical data from the ongoing open label Phase 1a dose escalation study of emavusertib (CA-4948), a novel, small molecule IRAK-4 inhibitor, as a monotherapy in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) or high risk myelodysplastic syndromes (hrMDS) in both targeted and non-targeted populations (Press release, Curis, DEC 12, 2022, View Source [SID1234625102]). Patients in a targeted population are those with disease harboring U2AF1, SF3B1 (collectively "spliceosome") or FLT3 mutations. The company also announced positive initial data of emavusertib in combination with venetoclax in patients with AML or hrMDS that enrolled in the combination phase (Phase 1b) of the TakeAim Leukemia study prior to the partial clinical hold placed in April 2022.

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"We have nearly doubled the size of the targeted patient data set, and continue to see consistent and deep anticancer activity, including additional objective responses. We believe these data suggest a favorable anti-cancer activity compared to therapies currently available for these patients. We are also encouraged by the initial combination data," said James Dentzer, President and Chief Executive Officer of Curis.

As of October 12, 2022, the total monotherapy data to date represents 24 response evaluable patients with a targeted mutation and 34 response evaluable patients without a targeted mutation. This represents 11 additional patients treated in targeted monotherapy populations and 13 additional patients in the non-targeted monotherapy population. In addition to the monotherapy data, there are 4 patients with AML/hrMDS who have been treated with emavusertib in combination with venetoclax.

In Expanded Data Set, Findings Support Earlier Data Presented in June 2021 and January 2022
Previous data presented by Curis highlighted preliminary efficacy data of emavusertib in R/R AML/MDS patients whose disease is characterized by spliceosome or FLT3 mutation. It is this genetically-defined subset of AML/MDS that is specifically targeted by emavusertib and which we believe, represents the patients most likely to benefit from treatment with emavusertib in monotherapy. Today’s clinical data update provides an expanded data set for this genetically-defined patient population.

In targeted AML patient monotherapy populations key findings included:

Patients with a FLT3 mutation had a CR (complete remission) rate of 29% (2 of 7 patients);
In addition to the 2 patients who achieved CRs, a 3rd patient achieved MLFS (morphologic leukemia-free state), and a 4th patient with gilteritinib-refractory disease achieved near normalization of blast count and complete loss of detectable FLT3 clone
Patients with a spliceosome mutation had CR/CRh rate of 22% (2 of 9 patients)
In targeted hrMDS patient monotherapy populations key findings included:

ORR (objective response rate) of 45% (5 of 11 patients)
All 5 responses achieved a marrow CR (mCR)
In combination AML/hrMDS patient populations key findings included:

ORR of 50% (2 of 4 patients)
Both responses achieved mCR
These data continue to confirm the earlier data that emavusertib provides favorable anti-cancer activity in AML and hrMDS patients with a spliceosome and/or FLT3 mutation. Further, anti-cancer activity in non-targeted patients as well as in combination with venetoclax suggest potential for incremental efficacy in combination with existing therapies. We are continuing to enroll patients at the 200mg dose level and plan to discuss with the U.S. Food and Drug Administration (FDA) a recommended phase 2 dose in mid-2023.

Conference Call Information
Curis management will host a conference call today, December 12, 2022 at 10:00 a.m. ET, to discuss the results with Dr. Eric Winer, Clinical Investigator at the Dana-Farber Cancer Institute. To access the live call, please dial (888) 346-6389 from the United States or (412) 317-5252 from other locations, shortly before 10:00 a.m. ET. A live webcast will be available under "Events & Presentations" in the Investors section of the Company’s website at www.curis.com. A replay of the webcast will be available on the Curis website shortly after completion of the call.

About emavusertib (CA-4948)
Emavusertib is an IRAK4 kinase inhibitor and IRAK4 plays an essential role in the toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways, which are frequently dysregulated in patients with cancer. TLRs and the IL-1R family signal through the adaptor protein MYD88, which results in the assembly and activation of IRAK4, initiating a signaling cascade that induces cytokine and survival factor expression mediated by the NF-κB protein complex. Additionally, third parties have recently discovered that the long form of IRAK4 (IRAK4-L) is oncogenic and preferentially expressed in over half of patients with AML and MDS. The overexpression of IRAK4-L is believed to be driven by a variety of factors, including specific spliceosome mutation such as SF3B1 and U2AF1. In addition to inhibiting IRAK4, emavusertib was also designed to inhibit FLT3, a known oncologic driver, which may provide additional benefit in patients with AML and MDS.

About TakeAim Studies
TakeAim Leukemia Study (NCT04278768) – This study is only enrolling in the monotherapy dose finding phase (phase 1a) of the study. The partial hold remains in place for the combination therapy phase (phase 1b) and expansion phase (phase 2a) of the study.

TakeAim Lymphoma Study (NCT03328078) – This study is open for enrollment.

On December 12, 2022 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported an update for both Part A and Part B of the Company’s ongoing Phase 1 CARBON trial evaluating the safety and efficacy of CTX110, its wholly-owned allogeneic CAR T cell therapy targeting CD19+ B-cell malignancies (Press release, CRISPR Therapeutics, DEC 12, 2022, View Source [SID1234625100]). Part A data, presented at ASH (Free ASH Whitepaper), showed the potential for CTX110 to achieve long-term durable complete remissions (CRs) with a positively differentiated safety profile in heavily pre-treated patients, and emerging data from Part B showed an encouraging efficacy profile with several patients in ongoing CR beyond six months.

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"We are excited by these results in our CARBON trial, which demonstrate the potential of a single course of allogeneic CAR T treatment to produce long-lasting complete remissions in heavily pre-treated patients with LBCL," said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. "Furthermore, we are encouraged by the emerging data using consolidation dosing, which has the potential to further improve the efficacy profile while maintaining a positively differentiated safety profile. Based on these results, we have initiated a potentially registrational Phase 2 trial of CTX110 incorporating consolidation dosing with the hope of bringing this important therapy to patients in the near term."

CARBON Trial Overview
The Phase 1 CARBON trial is an open-label, multicenter clinical trial evaluating the safety and efficacy of CTX110 in adult patients with relapsed or refractory CD19+ B-cell malignancies who have received at least two prior lines of therapy. To date, enrollment has been focused on patients with the most aggressive disease presentations, including Diffuse Large B-cell Lymphoma (DLBCL) not otherwise specified (NOS), high-grade double- or triple-hit lymphomas, transformed follicular lymphoma, and grade 3B follicular lymphoma. In Part A of the trial, patients were infused with a single dose of CTX110 following three days of a standard lymphodepletion regimen consisting of fludarabine (30mg/m2/day) and cyclophosphamide (500mg/m2/day). Patients received CTX110 at doses ranging from Dose Level (DL) 1 (30 million CAR+ T cells) to DL4 (600 million CAR+ T cells), with an option to re-dose CTX110 based on clinical benefit. In Part B of the trial, patients received CTX110 at DL4 following standard lymphodepletion, as well as a consolidation dose of CTX110 at the same dose level between four and eight weeks after the initial dose for patients that demonstrate clinical benefit. The primary endpoints include safety as measured by the incidence of dose limiting toxicities (DLTs) and overall response rate (ORR). Key secondary endpoints include complete response (CR) rate, duration of response (DOR) and overall survival (OS).

PART A

Data presented at ASH (Free ASH Whitepaper) (Poster #4629) show the potential for single infusions of CTX110 to achieve long-term durable complete remissions with a positively differentiated safety profile.

In a heavily pre-treated patient population with relapsed or refractory (R/R) LBCL (47% with ≥3 prior lines of therapy), CTX110 at DL≥3 (n=27) resulted in an ORR of 67% and CR rate of 41%.

Three patients remain in ongoing CR two years after treatment, and two additional patients remain in CR past one year.

No DLTs, no Graft versus Host Disease (GvHD) of any grade, and no Grade ≥3 cytokine release syndrome (CRS) events were observed.

These data formed the basis for Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA for CTX110, granted in November 2021.
PART B

Emerging data from Part B shows an encouraging efficacy profile with several patients in ongoing CR beyond six months.

Clear evidence of the benefits of consolidation dosing was observed, with deepening of CRs and conversions of stable disease and partial response to ongoing CRs after the second dose.

Safety profile remained consistent with Part A, confirming the tolerability of the consolidation regimen.

Peak expansion and overall pharmacokinetics of CTX110 were comparable between the initial and consolidation doses.

The Company plans to present additional Part B data at a future medical meeting.
Following discussions with regulatory agencies, the Company has initiated a single-arm, potentially registrational trial of CTX110, which incorporates consolidation dosing at DL4 and standard lymphodepletion. Dosing in this trial is expected to begin in early 2023 using drug product manufactured with a commercial-ready process and specifications.

About CTX110 and CARBON Trial

CTX110, a wholly owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR T investigational therapy targeting cluster of differentiation 19, or CD19. CTX110 is being investigated in the ongoing CARBON trial, a Phase 1 single-arm, multi-center, open label clinical trial, CARBON, is designed to assess the safety and efficacy of several dose levels of CTX110 for the treatment of relapsed or refractory B-cell malignancies. CTX110 has been granted RMAT designation by the FDA.

On December 12, 2022 Corvus Pharmaceuticals, Inc. (Corvus or the Company) (NASDAQ: CRVS), a clinical-stage biopharmaceutical company, reported updated results from its Phase 1/1b trial of CPI-818, the Company’s ITK inhibitor, which demonstrated its anti-tumor activity in patients with T cell lymphoma (TCL) and its therapeutic potential in Th2 and Th17-mediated autoimmune and allergic diseases (Press release, Corvus Pharmaceuticals, DEC 12, 2022, View Source [SID1234625099]). The data will be presented today in a poster at the 64TH American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, which is taking place in-person and virtually from December 10 to 13, 2022.

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"ITK inhibition with CPI-818 has demonstrated monotherapy anti-tumor activity in highly refractory T cell lymphoma patients, a population with limited and often ineffective treatment options," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "We have seen durable objective tumor responses in four of eleven evaluable patients. Based on the clinical results to-date, we plan to advance CPI-818 into a global Phase 2 clinical trial in T cell lymphoma in mid-2023. The study will be conducted in partnership with Angel Pharmaceuticals, which is responsible for the trial in China, where there is a higher incidence and prevalence of T cell lymphoma. The Phase 1 data also provided in vivo evidence of CPI-818’s ability to modulate immune functions of T cells by blocking both Th2 and Th17 T cells and skewing toward Th1 cells. The effects are important for cancer therapy – Th1 cells are essential for elimination of tumor cells – as well as in autoimmune and allergic diseases given that Th2 and Th17 cells are involved in many of these diseases. The clinical and preclinical findings reported at ASH (Free ASH Whitepaper) suggest that CPI-818 enhances anti-tumor immunity and represents a potential novel approach to immunotherapy. We are advancing CPI-818 across multiple therapeutic areas, starting with a Phase 1 clinical trial in atopic dermatitis, known to be a Th2 driven disease, planned for early 2023."

Dr. Miller concluded, "Overall, we believe the data presented at ASH (Free ASH Whitepaper) provides a strong foundation and rationale for ITK inhibition in lymphoma and certain immune diseases. CPI-818 is the most advanced ITK inhibitor we are aware of and has demonstrated high selectivity for ITK, which we believe has been crucial to achieving the immunomodulatory functions observed in our studies to date and represents a significant achievement of our research and development group. We look forward to providing updates on the development of CPI-818 and our other clinical programs – ciforadenant as a potential first line therapy for metastatic renal cell cancer and Angel Pharmaceutical’s study of mupadolimab in patients with relapsed refractory non-small cell lung cancer and head and neck squamous cell cancers – in the coming months and year."

CPI-818 Phase 1/1b Clinical Trial Key Results Presented at ASH (Free ASH Whitepaper) 2022
CPI-818 is being studied in a Phase 1/1b clinical trial as a single agent therapy in patients with relapsed TCL. As of September 2, 2022, 43 patients were enrolled in the trial across four escalating dosing cohorts: 100, 200, 400 and 600 mg, each being administered twice per day. The 200 mg dose was found to provide plasma drug concentrations that optimally affect T cell differentiation in vitro and correspondingly was found to lead to the most frequent and durable tumor responses in vivo. Accordingly, Corvus identified it as the optimal dose and additional patients are being enrolled in a 200 mg dose cohort of the clinical trial. The Phase 1/1b clinical trial endpoints are safety, pharmacokinetics (PK), immunologic effects and tumor response.

T Cell Lymphoma Interim Data Highlights

13 patients were enrolled in the 200 mg cohort and 11 were evaluable for response. Overall objective responses were seen in 4 of 11 patients. Enrolled patients were heavily pretreated receiving a median of 3 prior therapies. In this group, there was one complete response (CR) lasting 25 months in a patient with peripheral T cell lymphoma (PTCL); one nodal CR lasting 19 months in a patient with cutaneous T cell lymphoma; and two partial responses (PR) ongoing at six and eight months follow up, respectively, in patients with PTCL and anaplastic large cell lymphoma. An additional patient in the 600 mg cohort also had a PR.
No dose limiting toxicities were observed, and a maximally tolerated dose was not reached at doses as high as 600 mg twice per day.
All of the foregoing data was as of September 2, 2022.

Immunologic Effects Interim Data Highlights

As of September 2, 2022, the 200 mg optimal dose was shown to induce Th1 skewing and both Th2 and Th17 blockade based on peripheral blood samples from several patients:

In one patient that had a significant reduction of a large tumor on the abdominal wall, a blood sample analysis demonstrated an increase in blood Th1, a decrease in blood Th17, and a reduction of eosinophil count and IL-5 consistent with Th1 skewing and Th2 blockade. Tumor samples in this patient were also analyzed and showed an increase in terminally differentiated T effector memory cells (TEMRA cells), which are T cells that have responded to an antigen and are able to mediate effector functions, such as the destruction of tumor cells.
In four patients (two with PRs, one with stable disease (SD) and one with progressive disease (PD), the change in Th1 and CD8+ TEMRA cells was serially measured over time. The PR and SD patients showed an increase in both Th1 and CD8+ TEMRA cells. Of note, SD and PD patients were lymphopenic at baseline with absolute lymphocyte counts <1,000, highlighting the need for a minimal level of immune competence.

In vitro data demonstrated that CPI-818 induced Th1 skewing and Th2 blockade in a dose-dependent manner that supported the selection of the 200 mg dose. This includes an analysis of peripheral blood samples from 12 healthy volunteers that were stimulated in the presence of various concentrations of CPI-818 and other studies that showed that CPI-818 inhibited Th2 cytokine production from normal CD4+ and Sezary cells.
Other in vitro studies showed that CPI-818 inhibited the production of interleukin 4, 5 and 13 cytokines produced by Th2 cells.

In vivo preclinical studies in mice with transplanted T cell lymphoma showed that CPI-818 led to an increase in infiltration of normal CD8+ T cells in the tumor and inhibition of tumor growth.
The findings of the human and preclinical studies suggest that CPI-818 enhances anti-tumor immunity representing a potentially novel approach to immunotherapy.

Separate from the ASH (Free ASH Whitepaper) presentation, Corvus recently initiated a CPI-818 study in companion dogs with naturally occurring, refractory atopic dermatitis. Early results from this study demonstrated CPI-818’s potential activity in this disease with five out of five treated dogs responding to therapy within 14 days.
Conference Call, Webcast and Presentation Slides

Corvus will host a conference call and webcast today, Monday, December 12, 2022 from 4:30 – 5:30 pm ET to provide an overview of the CPI-818 data that presented at the ASH (Free ASH Whitepaper) meeting, along with providing an update on the Company’s development programs. The conference call can be accessed by dialing 1- 877-300-8521 (toll-free domestic) or 1- 412-317-6026 (international) and using the conference ID 10172958. The live webcast, which will include presentation slides, may be accessed via the investor relations section of the Corvus website. A replay of the webcast will be available on Corvus’ website for 90 days.