On December 9, 2019 Sanofi and Synthorx, Inc. (NASDAQ: THOR), a clinical-stage biotechnology company focused on prolonging and improving the lives of people suffering from cancer and autoimmune disorders, entered into a definitive agreement under which Sanofi will acquire all of the outstanding shares of Synthorx for $68 per share in cash, which represents an aggregate equity value of approximately $2.5 billion (on a fully diluted basis) (Press release, Sanofi, DEC 9, 2019, View Source [SID1234552083]). The transaction was unanimously approved by both the Sanofi and Synthorx Boards of Directors.

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"This acquisition fits perfectly with our strategy to build a portfolio of high-quality assets and to lead with innovation, as you will hear at our Capital Markets Day tomorrow, December 10. Additionally, it is aligned with our goal to build our oncology franchise with potentially practice-changing medicines and novel combinations," says Paul Hudson, Chief Executive Officer, Sanofi.

"Synthorx’s exceptionally novel discovery platform has already produced a molecule that has the potential to become a foundation of the next generation of immuno-oncology combination therapies. By selectively expanding the numbers of effector T-cells and natural killer cells in the body, THOR-707 can be combined with our current oncology medicines and our emerging pipeline of immuno-modulatory agents for treating cancer. Moreover, Synthorx’s pipeline of engineered lymphokines has great promise not only for oncology but also for addressing many autoimmune and inflammatory diseases. " says John Reed, M.D., Ph.D., Global Head of Research & Development at Sanofi.

"We are grateful that Sanofi has acknowledged the value of our Expanded Genetic Alphabet platform and the potential of our pipeline of optimized therapeutics for cancer and autoimmune disorders," says Laura Shawver, Ph.D., President and Chief Executive Officer, Synthorx. "Importantly, Sanofi has a portfolio of therapeutics that holds incredible promise for combining with our cytokine Synthorins to benefit patients around the world. I want to thank our employees and the Sanofi organization for their relentless efforts on behalf of patients."

Enhancing Sanofi’s Immuno-Oncology Franchise

Synthorx’s lead immuno-oncology product candidate, THOR-707, a variant of interleukin-2 (IL-2), is in clinical development in multiple solid tumor types as a single agent and in combination with immune checkpoint inhibitors. It has the potential to become the best-in-class IL-2 therapeutic for the treatment of solid tumors and demonstrate improved pharmacology, less frequent dosing, and therapeutic superiority when compared to other IL-2 compounds.

The addition of THOR-707 and Synthorx’s other earlier-stage cytokine programs to Sanofi’s pipeline will enhance Sanofi’s position in oncology, and in immuno-oncology. We expect IL-2 to become a foundation of future IO-IO combinations as well as offering multiple combination opportunities with Sanofi’s clinical and pre-clinical oncology assets, including with PD-1, CD-38, and molecules that modulate effector T-cells and natural killer cells.

Synergistic with Sanofi’s existing platforms

Synthorx’s Expanded Genetic Alphabet platform is expected to be a source for developing a differentiated therapeutic pipeline. Alone and in combination with other existing Sanofi platforms, including the Nanobody technology, it will enable the company to develop a wide range of novel biologics, including drug conjugates, protein fusions, and multi-specific biologics, with applications beyond oncology and extending to other therapeutic areas.

Transaction Terms

Under the terms of the merger agreement, Sanofi will commence a cash tender offer to acquire all of the outstanding shares of Synthorx common stock for $68 per share in cash for a total enterprise value of approximately $2.35 billion. The $68 per share acquisition price represents a 172% premium to Synthorx’s closing price on December 6, 2019.

The consummation of the tender offer is subject to customary closing conditions, including the tender of at least a majority of the outstanding shares of Synthorx common stock, the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, and other customary conditions. Following the successful completion of the tender offer, a wholly owned subsidiary of Sanofi will merge with Synthorx and the outstanding Synthorx shares not tendered in the tender offer will be converted into the right to receive the same $68 per share in cash paid in the tender offer. The tender offer is expected to commence in December 2019. Sanofi plans to finance the transaction with cash on hand. Subject to the satisfaction or waiver of customary closing conditions, Sanofi expects to complete the acquisition in the first quarter of 2020.

Morgan Stanley & Co. is acting as financial advisor to Sanofi and Weil, Gotshal & Manges LLP is acting as its legal counsel. Centerview Partners LLC is acting as exclusive financial advisor to Synthorx and Cooley LLP is acting as its legal counsel.

On December 9, 2019 Constellation Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, reported an update of preliminary data from the MANIFEST clinical trial in oral and poster presentations at the annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in Orlando (Press release, Constellation Pharmaceuticals, DEC 9, 2019, View Source [SID1234552110]).

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MANIFEST is an open-label Phase 2 clinical trial of the Company’s bromodomain and extra-terminal domain (BET) protein inhibitor CPI-0610 in patients with myelofibrosis (MF). Arm 3 is evaluating CPI-0610 in combination with ruxolitinib in JAK-inhibitor-naïve MF patients. Arms 1 and 2 are studying CPI-0610 as a monotherapy or in combination with ruxolitinib in ruxolitinib-resistant or -intolerant MF patients.

The updated preliminary data presented at ASH (Free ASH Whitepaper) showed signs of clinical activity for CPI-0610 similar to that previously reported at the annual meetings of the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) and the European Hematology Association (EHA) (Free EHA Whitepaper) and in the ASH (Free ASH Whitepaper) abstracts. The preliminary data included data on additional patients and showed evidence of activity across a broad range of myelofibrosis parameters in both JAK-inhibitor-naïve and ruxolitinib-resistant or -intolerant patients.

"If trends in preliminary data from MANIFEST in JAK-inhibitor-naïve patients are confirmed with further study, CPI-0610 has the potential to transform the standard of care in these patients," said Claire Harrison, D.M., Professor of Haematology, and Clinical Director, Guy’s and St Thomas’ NHS Foundation Trust, and a MANIFEST investigator.

"Preliminary data from MANIFEST in ruxolitinib-resistant or -intolerant patients are encouraging, suggesting the potential opportunity for a differentiated treatment option in such patients," said John Mascarenhas, M.D., Associate Professor, the Icahn School of Medicine at Mount Sinai, and a MANIFEST investigator.

The presentations at ASH (Free ASH Whitepaper) reflect data as of an October 17, 2019, data cutoff, updating preliminary data presented in ASH (Free ASH Whitepaper) abstracts published on November 6, 2019, as of a June 27, 2019, data cutoff.

Below are highlights of the presentations at ASH (Free ASH Whitepaper):

JAK-Inhibitor-Naïve Patients (Arm 3)

SVR35: Twelve out of 15 (80%) evaluable JAK-inhibitor-naïve patients experienced SVR35 at 12 weeks. The median percent change in spleen volume reduction was -49.7%.
TSS50: Ten out of 14 (71%) evaluable patients achieved at least a 50% improvement in Total Symptom Score (TSS50) at 12 weeks. The median percent change in TSS at 12 weeks was -60.3%.
Ruxolitinib-Resistant or -Intolerant Patients (Arms 1 and 2)

CPI-0610 Add-on to Ruxolitinib in Transfusion-Dependent Patients (Cohort 2A)

SVR35: At 24 weeks, SVR35 was achieved in 3 out of 12 (25%) evaluable patients, with a median percent change of -24.9%. An SVR35 at any time (best response) was achieved in 5 out of 17 (29%) evaluable patients, with a best median percent change of -21.2%.
SVR: At 24 weeks, 11 out of 12 (92%) evaluable patients had a spleen volume reduction.
TSS50: At 24 weeks, TSS50 was achieved in 7 out of 13 (54%) evaluable patients, with a median percent change of -58.8%. A TSS50 at any time (best response) was achieved in 13 out of 17 (76.5%) evaluable patients, with a median best change of -71.0%.
TD to TI: Conversion from transfusion dependence (TD) to transfusion independence (TI) occurred in 6 out of 14 (43%) evaluable patients with at least 24 weeks of treatment.
Other Ruxolitinib-Resistant or -Intolerant Patients (Cohorts 1A, 1B, and 2B)

SVR35: None of the patients in these cohorts achieved SVR35 at 24 weeks. An SVR35 at any time (best response) was achieved in 1 out of 4 evaluable patients in cohort 1A.
SVR: Nine out of 13 (69%) evaluable patients in Cohort 2B, 1 out of 2 (50%) evaluable patients in Cohort 1A, and 5 out of 7 (71%) evaluable patients in Cohort 1B achieved a spleen volume reduction at 24 weeks. The median reductions were -10.9%, -3.2%, and -26.0%, respectively.
TSS50: Five out of 13 (38%) evaluable patients in Cohort 2B, 0 out of 1 evaluable patient in Cohort 1A, and 3 out of 5 (60%) evaluable patients in Cohort 1B achieved a TSS50 at 24 weeks. Median reductions were -44.1%, -18.4%, and -53.5%, respectively.
TD to TI: Zero out of 2 TD patients in cohort 1A with at least 24 weeks of treatment converted to TI.
Additional Data Supporting Possible Disease Modification

Hemoglobin Improvement: Six out of 11 (55%) evaluable patients treated with CPI-0610 monotherapy and 2 out of 15 (13%) evaluable patients treated with CPI-0610 + ruxolitinib achieved at least a 1.5 g/dL improvement in hemoglobin without receiving a blood transfusion in the 12 weeks prior to assessment.
Bone Marrow Fibrosis Score Improvement: Twelve out of 32 (38%) evaluable patients in Arms 1 and 2, including 7 out 11 (63%) evaluable patients in Cohort 2A, achieved at least a one-grade improvement in bone marrow fibrosis score. Ten out of 12 improvements occurred within the first six months of treatment.
Safety

CPI-0610 in combination with ruxolitinib in JAK-inhibitor-naïve patients (Arm 3) was generally well tolerated. No adverse events led to study discontinuation. Three patients (10%) had ≥ Grade 3 anemia. One patient (3.3%) had Grade 4 thrombocytopenia, which was reversible. The most common non-hematologic adverse events were diarrhea, nausea, dizziness, and muscle spasms, which were primarily Grade 1/2.
CPI-0610 as monotherapy or in combination with ruxolitinib in ruxolitinib-refractory or -intolerant patients (Arms 1 and 2) was generally well tolerated. The most common hematologic adverse event was thrombocytopenia. Nine patients (10%) had ≥ Grade 3 thrombocytopenia, none of which were serious adverse events. These nine patients included two (5.6%) in Arm 1 and seven (12.9%) in Arm 2. The most common non-hematologic adverse events, primarily Grade 1/2, were diarrhea, nausea, cough, fatigue, vomiting, and upper respiratory tract infection. Eight out of 90 (8.9%) patients reported Grade 4 adverse events, all of which resolved. Of these eight, four (11.1%) occurred in Arm 1, of which three required dose interruption and one (rash) was considered related to CPI-0610, and four (7.4%) occurred in Arm 2, none required dose reduction and one (anemia) was considered related to the combination therapy. One ruxolitinib-resistant or -intolerant patient (1.1%) discontinued due to serious adverse event(s), which were reported as unlikely to have been related to CPI-0610. Three out of 90 (3.3%) ruxolitinib-resistant or -intolerant patients, all in Arm 2, reported Grade 5 adverse events—acute kidney injury, traumatic subdural hematoma (fall due to tripping), and brain stem hemorrhage (no concomitant thrombocytopenia)—none of which were considered by Constellation to be related to CPI-0610.
Orphan Drug Designation

The U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to CPI-0610 for the treatment of MF on November 20, 2019.
The FDA Orphan Drug Designation program provides orphan status to drugs and biologics that are defined as those intended for the safe and effective treatment, diagnosis, or prevention of rare diseases or disorders that affect fewer than 200,000 people in the United States. Under specified conditions, this designation may provide companies a seven-year marketing exclusivity period, as well as certain incentives, including federal grants, tax credits, and a waiver of Prescription Drug User Fee Act (PDUFA) filing fees.
Future Plans

Constellation continues to enroll patients in MANIFEST. As a result of encouraging preliminary data, Constellation expanded Arm 3 of MANIFEST for JAK-inhibitor-naïve patients from 43 to up to 101 patients. The Company also expanded Cohort 2A, for TD ruxolitinib-resistant or -intolerant patients adding CPI-0610 to ruxolitinib, from 16 to up to 60 patients.
Constellation has started planning for a randomized, active-controlled, pivotal Phase 3 clinical trial studying the combination of CPI-0610 and ruxolitinib versus ruxolitinib and placebo in JAK-inhibitor-naïve patients with MF. The Company expects this clinical trial to start in 2020.
Investor Event

Constellation will host an analyst/investor event and webcast today at 12:30 PM EST in Salon 2 at the Rosen Centre Hotel in Orlando in conjunction with the annual meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper). The event will be webcast live and can be accessed on the Investor Relations section of Constellation’s website at View Source Analysts and investors may also access the event and participate in the live question-and-answer session by dialing (877) 473-2077 (domestic) or (661) 378-9662 (international) and referring to conference ID 7892044. A replay of the call will be available at (855) 859-2056, (404) 537-3406, or (800) 585-8367.
About MANIFEST

MANIFEST is an open-label Phase 2 clinical trial of CPI-0610 in patients with myelofibrosis (MF), a rare cancer of the bone marrow that disrupts the body’s normal production of blood cells. Constellation is evaluating CPI-0610 in combination with ruxolitinib in JAK-inhibitor-naïve MF patients (Arm 3), with a primary endpoint of the proportion of patients with a ≥35% spleen volume reduction from baseline after 24 weeks of treatment. Constellation is also evaluating CPI-0610, either as a monotherapy in patients who are resistant to, intolerant of, or ineligible for ruxolitinib and no longer on the drug (Arm 1), or as add-on therapy in combination with ruxolitinib in patients with a sub-optimal response to ruxolitinib or MF progression (Arm 2). Patients in Arms 1 and 2 are being stratified based on TD status. The primary endpoint for the patients in cohorts 1A and 2A, who were TD at baseline, is conversion to TI for 12 consecutive weeks. The primary endpoint for the patients in cohorts 1B and 2B, who were not TD at baseline, is the proportion of patients with a ≥35% spleen volume reduction from baseline after 24 weeks of treatment.

On December 9, 2019 Quest Diagnostics Incorporated (NYSE: DGX), the world’s leading provider of diagnostic information services, reported the pricing of a public offering of $800 million aggregate principal amount of its 2.950% senior notes due 2030 under the Quest Diagnostics’ shelf registration statement (Press release, Quest Diagnostics, DEC 9, 2019, View Source [SID1234552127]).

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Quest Diagnostics expects to receive the net offering proceeds upon closing on December 16, 2019, subject to customary closing conditions. The company intends to use the net proceeds from the offering to repay at maturity or redeem its 4.750% senior notes due 2020 and 2.500% senior notes due 2020 and for general corporate purposes. This press release is not a notice of redemption. Any notice of redemption will be made in accordance with the applicable provisions of the indenture governing such notes.

This press release shall not constitute an offer to sell or a solicitation of an offer to purchase any of these securities and shall not constitute an offer, solicitation or sale in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful. This offering may be made only by means of a prospectus supplement and accompanying base prospectus, copies of which or information concerning this offering may be obtained by calling J.P. Morgan Securities LLC, collect at (212) 834-4533, Morgan Stanley & Co. LLC, toll-free at (866) 718-1649 or Wells Fargo Securities, LLC, toll-free at (800) 645-3751.

On December 9, 2019 Gamida Cell Ltd. (Nasdaq: GMDA), an advanced cell therapy company committed to finding cures for blood cancers and serious blood diseases, reported updated results from a Phase 1 clinical study of GDA-201, an investigational, natural killer (NK) cell-based cancer immunotherapy for the treatment of patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM), at the 61st Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper), which is being held December 7–10 in Orlando, FL (Press release, Gamida Cell, DEC 9, 2019, View Source [SID1234552145]). Data from 22 patients in the ongoing study showed GDA-201 in combination with monoclonal antibodies was generally well tolerated and demonstrated early evidence of clinical activity in heavily pre-treated patients, including five complete responses observed among nine patients with NHL. Gamida Cell plans to initiate a Phase 1/2 multi-dose, multi-center study of GDA-201 in patients with NHL in 2020.

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"NK cells are increasingly recognized as a potential breakthrough approach in immunotherapy, and the data reported today provide early evidence that GDA-201 has the potential to be an important new treatment option," said Veronica Bachanova, M.D., Ph.D., Associate Professor of Medicine in the Division of Hematology, Oncology and Transplantation at the University of Minnesota and principal investigator of the study through the Masonic Cancer Center. "Given the population of heavily pre-treated patients with advanced disease, it’s particularly encouraging to witness multiple complete responses. I look forward to the continued development of this investigational therapy."

New research was also presented today on the mechanism of action of Gamida Cell’s NAM-based cell expansion platform, which is designed to enhance the number and functionality of allogeneic donor cells. These data provide further scientific rationale for the favorable stem cell engraftment and patient outcomes observed in the Phase 1/2 clinical study of omidubicel, the company’s advanced cell therapy currently in Phase 3 clinical development as a potential life-saving treatment option for patients in need of an allogeneic bone marrow transplant.

"These mechanism of action data reinforce the transformative potential of our NAM therapeutic platform, which can be used to expand multiple cell types. Specifically for omidubicel, this research suggests that NAM modulates certain gene expression pathways that, collectively, mimic the hypoxic environment of the bone marrow to help preserve stem cell function and long-term engraftment ability," said Tracey Lodie, Ph.D., chief scientific officer of Gamida Cell. "We expect to build on our findings by characterizing the metabolites produced when we expand stem cells to make omidubicel, and we are also beginning to conduct similar mechanism of action studies with GDA-201."

GDA-201 Phase 1 Clinical Data Presented at ASH (Free ASH Whitepaper)

The oral presentation, "Results of a Phase 1 Trial of GDA-201, Nicotinamide-Expanded Allogeneic Natural Killer Cells (NAM-NK) in Patients with Refractory Non-Hodgkin Lymphoma (NHL) and Multiple Myeloma (MM)" (Abstract #777), described data from the Phase 1 clinical study of GDA-201 in heavily pre-treated patients with advanced NHL and MM. Twenty-two patients were enrolled in the study, including nine patients with NHL and 13 patients with MM. Of these 22 patients, all were evaluable for safety and 21 were evaluable for response (NHL = 9; MM = 12).

In the study, cell therapy using GDA-201 with monoclonal antibodies was generally well tolerated and demonstrated early evidence of clinical activity. Of the nine patients with NHL, five achieved a complete response and one achieved a partial response. Among the patients with MM, one patient achieved a complete response, and five patients achieved stable disease.

GDA-201 was generally well tolerated, with no graft vs. host disease (GvHD), no tumor lysis syndrome, no neurotoxicity and no marrow aplasia observed. No dose limiting toxicities were observed. Hypertension and hematologic events were the most common Grade 3/4 adverse events observed. Most non-hematologic toxicities were attributed to cyclophosphamide/fludarabine, which was used as a pre-conditioning treatment.

NAM Therapeutic Platform Mechanism of Action Data Presented at ASH (Free ASH Whitepaper)

The poster presentation, "Nicotinamide (NAM) Modulates Transcriptional Signature of Ex Vivo Cultured UCB CD34+ Cells (Omidubicel) and Preserves Their Stemness and Engraftment Potential" (Abstract #3718), included transcriptome, transcription factor, and pathway analysis to elucidate the pathways leading to the preservation of engraftment after ex vivo expansion of CD34+ hematopoietic stem cells derived from umbilical cord blood (the starting point for omidubicel) compared to CD34+ cells grown in the absence of NAM.

Analyses showed that the presence of NAM reduced the expression of genes involved in the production of reactive oxygen and nitrogen species, suggesting that cell stress was minimized during expansion. In addition, NAM also decreased growth factor pathways responsible for activation and differentiation of hematopoietic stem cells, suggesting NAM expanded cells while keeping them in an undifferentiated state. The presence of NAM also led to a decrease in the expression of genes responsible for matrix-metallo proteinase secretion, simulating the microenvironment of the bone marrow. Additionally, NAM led to an increased expression of telomerase genes, which is believed to enable cells to remain in a more quiescent, stem-like state. These data provide further scientific rationale for the favorable stem cell engraftment and patient outcomes that were observed in the Phase 1/2 clinical study of omidubicel.

About GDA-201
GDA-201 (formerly known as NAM-NK) is being developed as an innate natural killer (NK) cell immunotherapy for the treatment of hematologic and solid tumors in combination with standard-of-care antibody therapies. NK cells have the ability to kill tumor cells, representing a novel immunotherapeutic approach to cancer treatment. GDA-201 is designed to address key limitations of NK cells by increasing the cytotoxicity and in vivo retention and proliferation in the bone marrow and lymphoid organs of NK cells expanded in culture. GDA-201 is in Phase 1 development in patients with refractory non-Hodgkin lymphoma and multiple myeloma.1 For more information on the clinical study of GDA-201, please visit www.clinicaltrials.gov.

About Omidubicel
Omidubicel (formerly known as NiCord), the company’s lead clinical program, is an advanced cell therapy under development as a potential life-saving allogeneic hematopoietic stem cell (bone marrow) transplant solution for patients with hematologic malignancies (blood cancers). Omidubicel is the first bone marrow transplant product to receive Breakthrough Therapy Designation from the U.S. Food and Drug Administration and has also received Orphan Drug Designation in the U.S. and EU. In a Phase 1/2 clinical study, omidubicel demonstrated rapid and durable time to engraftment and was generally well tolerated.2 A Phase 3 study evaluating omidubicel in patients with leukemia and lymphoma is ongoing in the U.S., Latin America, Europe and Asia.3 Omidubicel is also being evaluated in a Phase 1/2 clinical study in patients with severe aplastic anemia.4 The aplastic anemia investigational new drug application is currently filed with the FDA under the brand name CordIn, which is the same investigational development candidate as omidubicel. For more information on clinical trials of omidubicel, please visit www.clinicaltrials.gov.

GDA-201 and omidubicel are investigational therapies, and their safety and efficacy have not been evaluated by the U.S. Food and Drug Administration or any other health authority.

About the NAM Therapeutic Platform
Gamida Cell’s proprietary NAM-based cell expansion platform is designed to enhance the number and functionality of donor cells in culture, enabling the creation of potentially transformative therapies that move beyond what is possible with existing approaches. The NAM therapeutic platform leverages the unique properties of nicotinamide to enable the expansion of multiple cell types — including stem cells and natural killer (NK) cells — with appropriate growth factors to maintain the cells’ original phenotype and potency. This can enable the administration of a therapeutic dose of cells with the potential to improve patient outcomes.

On December 9, 2019 Kymera Therapeutics Inc., a biotechnology company pioneering targeted protein degradation to discover breakthrough medicines for patients, reported the company will present new preclinical data showing the further characterization of novel, highly selective and potent degraders of STAT3 with activity across multiple hematologic malignancies including ALK-positive anaplastic large cell lymphoma (ALK+ ALCL), acute myelogenous leukemia (AML) and diffuse large B cell lymphoma (DLBCL) (Press release, Kymera Therapeutics, DEC 9, 2019, View Source [SID1234552161]). Data will be shared during a poster presentation (Abstract #3803) at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando on Monday, Dec. 9 at 6:00 PM EST in Orange County Convention Center, Hall B, Level 2.

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STAT3 is an oncogenic transcription factor downstream of multiple signaling events including the IL-6/JAK and ALK pathways. Activating mutations and aberrant activation of STAT3 drive a subset of tumors via induction of autocrine factors that promote tumor proliferation and survival, as well as induction of proteins that contribute to a tumor permissive microenvironment. Degrading STAT3 has been shown to disrupt downstream signaling and induce antitumor responses in STAT3-dependent hematologic malignancies.

"As Kymera advances our STAT3 degraders into the clinic, we continue to expand the characterization of the biological impact of STAT3 degradation in liquid and solid tumors including the pharmacodynamic effect required to achieve complete tumor regression in a mouse xenograft model of ALK+ ALCL," said Jared Gollob, MD, CMO of Kymera Therapeutics. "These data highlight the potential for STAT3 degraders to treat STAT3-dependent lymphomas and leukemias, and enable the rational development of a treatment regimen that maximizes the probability of success in patients. We plan to select a lead STAT3 degrader for IND-enabling studies in 2020."

ASH Study Highlights
ABSTRACT #3803, "Small Molecule-Induced, Selective STAT3 Degradation Leads to Anti-Tumor Activity in STAT3-Dependent Heme Malignancies," presented by Fred Csibi, PhD, Associate Director, Oncology Biology at Kymera Therapeutics.

KYM-003 treatment resulted in rapid, potent and highly selective STAT3 degradation with similar activity against both mutant and wild-type STAT3.
KYM-003 repressed the growth in vitro of multiple ALK+ ALCL cell lines as well as AML and DLBCL.
Sustained STAT3 degradation of 90% or greater led to apoptosis induction and cancer cell death within 48hr in vitro and in vivo.
Intermittent dosing of KYM-003 achieved complete tumor regression in an ALK+ ALCL mouse xenograft model.