On October 7, 2021 Seagen Inc. (Nasdaq: SGEN) reported that it will report its third quarter 2021 financial results on Thursday, October 28, 2021 after the close of U.S. financial markets. Following the announcement, Company management will host a conference call and webcast that day at 4:30 p.m. Eastern Time to discuss the results and provide a business update. Access to the event can be obtained as follows (Press release, Seagen, OCT 7, 2021, View Source [SID1234590941]):

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Telephone 844-763-8274 (U.S.) or +1 412-717-9224 (international); conference ID 10160629
Webcast with slides can be accessed at investor.seagen.com. A webcast replay will be archived on the Company’s website.

On October 7, 2021 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported results from a retrospective analysis of the pooled results of three randomized trilaciclib studies showing that patients with extensive-stage small-cell lung cancer (ES-SCLC) who received the drug prior to each chemotherapy treatment had significantly lower use of supportive care therapies for chemotherapy-induced myelosuppression than patients who received placebo (Press release, G1 Therapeutics, OCT 7, 2021, View Source [SID1234590940]). Results of the retrospective analysis are published in the online edition of the journal Cancer Medicine.

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COSELA (trilaciclib) is indicated to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer.

In the study, the researchers assessed the impact of trilaciclib versus placebo on subsequent use of supportive therapies—including granulocyte colony stimulating factor (G-CSF), erythropoiesis-stimulating agents (ESAs), and red blood cell transfusions—following chemotherapy treatments for ES-SCLC. The results showed that trilaciclib significantly reduced the duration and occurrence of chemotherapy-induced severe neutropenia and the occurrence of grade 3 or greater chemotherapy-induced anemia, with a corresponding reduction in the use of supportive care therapies to manage these adverse events.

The publication titled, "Trilaciclib Prior to Chemotherapy Reduces the Usage of Supportive Care Interventions for Chemotherapy-Induced Myelosuppression in Patients with Small Cell Lung Cancer: Pooled Analysis of Three Randomized Phase 2 Trials," can be accessed here.

Specifically, the analysis showed that administering trilaciclib prior to chemotherapy:

Significantly reduced the occurrence of severe neutropenia—11.4% in the trilaciclib group versus 52.9% in the placebo group (p < 0.0001).
with a corresponding reduction in G-CSF use by approximately half in the trilaciclib group compared with placebo
Consistency of treatment effects on occurrence of severe neutropenia with or without concomitant G-CSF use was tested and results indicated that the effect of trilaciclib was consistent regardless of whether or not a G-CSF was administered.
Significantly reduced the occurrence of grade 3/4 anemia compared with placebo—20.3% in the trilaciclib group versus 31.9% in the placebo group (p = 0.0279)
with a corresponding reduction of ESA treatment: 3.3% trilaciclib versus 11.8% placebo (p = 0.0254)
and a corresponding reduction of red blood cell transfusions on or after week five: 14.6% trilaciclib versus 26.1% placebo (p = 0.0252)
In a separate analysis, the use of trilaciclib significantly reduced patient hospitalizations due to chemotherapy induced myelosuppression (CIM) or sepsis, with 4.1% of patients hospitalized in the trilaciclib arm versus 13.6% of patients hospitalized in the placebo arm
The findings were derived from a retrospective analysis of pooled data obtained from three randomized, Phase 2 clinical trials of trilaciclib or placebo administered prior to chemotherapy in 242 patients with ES-SCLC. The authors suggest that the pooled data indicate that the administration of trilaciclib prior to chemotherapy has the potential to reduce the burden of CIM on health care systems.

"The results from our analysis show clear myeloprotection benefits associated with the administration of trilaciclib prior to chemotherapy in patients with ES-SCLC," said Renata Ferrarotto, MD, Associate Professor, Department of Thoracic/Head and Neck Medical Oncology at MD Anderson Cancer Center and lead author of the study. "By reducing the need for associated supportive care, trilaciclib has the potential to reduce both the societal and economic burden of chemotherapy-induced myelosuppression."

Chemotherapy-induced myelosuppression (CIM) is one of the most common, dose-limiting complications of cancer treatment, and is associated with a range of symptoms that can significantly impact patients’ quality of life. The researchers concluded that "trilaciclib may help to reduce the burden of chemotherapy-induced myelosuppression on patients, caregivers, and health care systems."

About Small Cell Lung Cancer
In the United States, approximately 30,000 small cell lung cancer patients are treated annually. SCLC, one of the two main types of lung cancer, accounts for about 10% to 15% of all lung cancers. SCLC is an aggressive disease and tends to grow and spread faster than NSCLC. It is usually asymptomatic; once symptoms do appear, it often indicates that the cancer has spread to other parts of the body. About 70% of people with SCLC will have cancer that has metastasized at the time they are diagnosed. The severity of symptoms usually increases with increased cancer growth and spread. From the time of diagnosis, the general 5-year survival rate for people with SCLC is 6%. The five-year survival rates for limited-stage (the cancer is confined to one side of the chest) SCLC is 12% to 15%, and for extensive stage (cancer has spread to the other lung and beyond), survival rates are less than 2%. Chemotherapy is the most common treatment for ES-SCLC.

About COSELA (trilaciclib) for Injection

COSELA (trilaciclib) was approved by the U.S. Food and Drug Administration on February 12, 2021.

Indication
COSELA (trilaciclib) is indicated to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer.

Select Important Safety Information

CONTRAINDICATION
COSELA is contraindicated in patients with a history of serious hypersensitivity reactions to trilaciclib.

WARNINGS AND PRECAUTIONS
Injection-Site Reactions, Including Phlebitis and Thrombophlebitis
COSELA administration can cause injection-site reactions, including phlebitis and thrombophlebitis, which occurred in 56 (21%) of 272 patients receiving COSELA in clinical trials, including Grade 2 (10%) and Grade 3 (0.4%) adverse reactions. Injection-site reactions led to discontinuation of treatment in 3 (1%) of the 272 patients.

Acute Drug Hypersensitivity Reactions
COSELA administration can cause acute drug hypersensitivity reactions, which occurred in 16 (6%) of 272 patients receiving COSELA in clinical trials, including Grade 2 reactions (2%).

Interstitial Lung Disease/Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with cyclin-dependent kinases (CDK)4/6 inhibitors, including COSELA, with which it occurred in 1 (0.4%) of 272 patients receiving COSELA in clinical trials.

Embryo-Fetal Toxicity
Based on its mechanism of action, COSELA can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should use an effective method of contraception during treatment with COSELA and for at least 3 weeks after the final dose.

ADVERSE REACTIONS
The most common adverse reactions (≥10%) were fatigue, hypocalcemia, hypokalemia, hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia.

Serious adverse reactions occurred in 30% of patients receiving COSELA. Serious adverse reactions reported in >3% of patients who received COSELA included respiratory failure, hemorrhage, and thrombosis. Fatal adverse reactions were observed in 5% of patients receiving COSELA. Fatal adverse reactions for patients receiving COSELA included pneumonia (2%), respiratory failure (2%), acute respiratory failure (<1%), hemoptysis (<1%), and cerebrovascular accident (<1%).

This information is not comprehensive. Please click here for full Prescribing Information. View Source

To report suspected adverse reactions, contact G1 Therapeutics at 1-800-790-G1TX or call FDA at 1-800-FDA-1088 or visit www.fda.gov/medwatch.

On October 7, 2021 Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported that XMT-2056, its first Immunosynthen STING-agonist ADC candidate, targets a novel epitope of human epidermal growth factor receptor 2 (HER2) and presented new preclinical data during a plenary session at the AACR (Free AACR Whitepaper)-NCI-EORTC Virtual AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) (Triple Meeting) (Press release, Mersana Therapeutics, OCT 7, 2021, View Source [SID1234590939]).

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"Previously, across multiple targets and models, we demonstrated that our Immunosynthen ADCs can stimulate the innate immune system in a targeted manner in both tumor cells and tumor-resident myeloid cells – a "one-two punch" resulting in robust efficacy. New head-to-head preclinical data comparing XMT-2056 to TLR7/8-agonist ADC and systemically-administered STING agonist benchmarks further supports the potential advantages of XMT-2056 to offer greater efficacy and a wider therapeutic index," said Timothy B. Lowinger, PhD, Chief Science and Technology Officer of Mersana Therapeutics. "In addition, new data with XMT-2056 in combination with trastuzumab supports our rationale for selecting an antibody that recognizes a novel epitope of HER2, providing broad combination potential with approved and investigational HER2 therapies."

"STING is a fundamental mechanism yet approaches to date have been unsuccessful at stimulating the innate immune system in a targeted manner. Our Immunosynthen platform not only has the potential to address this limitation but also is designed to allow us to extend our ADC development efforts beyond cytotoxic payloads, which we believe represents a significant advancement in the ADC field," said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. "We are particularly excited about the potential of XMT-2056 to offer a novel approach to the treatment of HER2-expressing tumors both as a single agent and in combination."

Previously reported preclinical data suggest that XMT-2056 offers a highly differentiated approach, enabling tumor-targeted delivery of a STING agonist with improved efficacy and tolerability over a systemically-administered STING agonist benchmark. In vitro and in vivo studies demonstrate that STING-agonist ADCs activate the STING pathway in both tumor-resident immune cells and tumor cells, offering the potential for an increased therapeutic index and an advantage over other innate immune activating pathways.

The Company has evaluated Immunosynthen ADCs across a wide range of antibodies, targets, tumor models and mouse strains and observed broad efficacy and consistent results demonstrating target-dependent anti-tumor effects and has selected HER2 as the first target for clinical evaluation with XMT-2056. The Company developed a differentiated anti-HER2 antibody that binds a novel epitope distinct from that of trastuzumab and pertuzumab, providing the opportunity for combinations with these well-established anti-HER2 therapies.

New preclinical data presented today at the Triple Meeting include:

XMT-2056 demonstrated increased efficacy in both high and low HER2 SCID mouse models in comparison to benchmark agents such as a trastuzumab-TLR7/8 agonist ADC as well as a small molecule systemically-administered STING agonist.
XMT-2056 showed excellent in vivo efficacy as a single agent in a SKOV3 HER2 high model and this efficacy is further enhanced by combining XMT-2056 with a 3 mg/kg dose of trastuzumab.
XMT-2056 was generally well-tolerated in NHP studies with no clinical signs and no adverse findings in clinical pathology or histopathology after single and repeat IV doses of 9 mg/kg, at exposures far exceeding those necessary for efficacy in mouse models, indicating the potential for a wide therapeutic index.

On October 7, 2021 Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer (NK) cell therapies to treat cancer, reported NKX019 and NKX101 clinical development program updates (Press release, Nkarta, OCT 7, 2021, View Source [SID1234590938]).

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Patients have been dosed in the international Phase 1 clinical trial of NKX019 in advanced B-cell malignancies. NKX019 is an NK cell immunotherapy that is engineered to eradicate tumors expressing CD19, a validated B-cell cancer target.

"We are excited to explore the potential of NKX019, our second clinical-stage, engineered chimeric antigen receptor (CAR) NK cell therapy candidate, to become a leading treatment of B-cell malignances for eventual use in a broadly accessible outpatient setting," said Paul J. Hastings, President and Chief Executive Officer of Nkarta. "NKX019 builds upon the potent innate anti-tumor biology and promising safety profile of natural killer cells. This trial moves us one step closer to bringing game-changing, off-the-shelf cell therapies to cancer patients. We anticipate reporting initial data from the NKX019 study in 2022."

Nkarta is producing the clinical supply of NKX019 at its in-house cGMP clinical manufacturing facility in South San Francisco, California.

Nkarta is also updating guidance on when it expects to announce initial data from the first-in-human Phase 1 clinical trial of NKX101, an engineered CAR NK cell therapy candidate targeting the NKG2D ligand, in patients with relapsed or refractory acute myeloid leukemia (AML) or higher-risk myelodysplastic syndromes (MDS) to the first half of 2022.

Multiple factors have affected the cadence of the NKX101 Phase 1 study, including the use of haplomatched donor derived cells in the original study design, requirement for a staggered enrollment of patients that was longer than originally expected, and COVID-19 related disruptions. As previously announced, the clinical trial protocol was later amended in consultation with the U.S. Food and Drug Administration to be able to dose patients with either off-the-shelf or haplomatched cells, shorten the stagger between certain patients, and introduce a second parallel dosing regimen. The new timing is intended to allow Nkarta to report a robust data set from the study, which is currently enrolling patients at several locations in the United States.

About the NKX019-101 Clinical Trial
The NKX019-101 clinical trial is a Phase 1, multi-center, open-label, dose-finding and dose-expansion study to evaluate the safety and anti-tumor activity of NKX019 as a multi-dose, multi-cycle monotherapy. Patients with CAR T naïve relapsed/refractory non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) or B-cell acute lymphoblastic leukemia (B-ALL) will be enrolled in the dose-finding portion of the study. Following the selection of a recommended Phase 2 dose, patients with r/r B-ALL, CLL, or other subtypes of NHL, including patients who did not achieve a durable response after treatment with a CD19 CAR T cell therapy, will be enrolled in the dose-expansion portion of the trial. To learn more about the clinical trial of NKX019 in advanced B cell malignancies, please visit ClinicalTrials.gov.

About NKX019
NKX019 is an investigational, allogeneic, off-the-shelf cancer immunotherapy that uses natural killer (NK) cells derived from the peripheral blood of healthy adult donors. It is engineered with a humanized CD19-directed CAR for enhanced tumor cell targeting and a proprietary, membrane-bound form of interleukin-15 (IL-15) for greater persistence and activity without exogenous cytokine support. CD19 is a biomarker for normal and malignant B cells, and it is a validated target for B cell cancer therapies.

About NKX101
NKX101 is an investigational, off-the-shelf cancer immunotherapy that uses natural killer (NK) cells derived from the peripheral blood of healthy donors and engineered with membrane-bound IL-15 and a chimeric antigen receptor (CAR) targeting NKG2D ligands on tumor cells. NKG2D, a key activating receptor found on naturally occurring NK cells, induces a cell-killing immune response through the detection of stress ligands that are widely expressed on cancer cells. By engineering NKX101 with the proprietary NKG2D-based CAR, the ability of NK cells to recognize and kill tumor cells in pre-clinical models is increased significantly compared to non-engineered NK cells. The addition of membrane-bound IL15, a proprietary version of a cytokine for activating NK cell growth, has been shown in pre-clinical models to enhance the proliferation, persistence and sustained activity of NK cells. To learn more about the NKX101 clinical trial in adults with AML or MDS, please visit ClinicalTrials.gov.

About B-Cell Cancers
B-cell lineage cancers are a worldwide healthcare burden. Over 500,000 new cases of non-Hodgkin lymphoma (NHL) and 50,000 new cases of acute lymphoblastic leukemia (ALL) are diagnosed world-wide each year (seer.cancer.gov, Smith 2015, Solomon 2017). Despite progress in treatment, many patients diagnosed with this heterogeneous group of cancers still succumb to their diseases. Autologous chimeric antigen receptor (CAR) T cells specific for CD19 have altered the treatment landscape for some patients with relapsed or refractory B-cell malignancies, though significant toxicities associated with T-cell expansion and the necessity for bespoke manufacturing have limited their use.

About AML and MDS
Acute Myeloid Leukemia (AML) is a rapidly progressing blood cancer caused by abnormalities of myeloid cells, a cell type in the bone marrow that would normally develop into different types of blood cells. AML usually worsens rapidly and can lead to death if not treated. Over 120,000 new cases of AML are diagnosed world-wide each year.* Despite recent advancements, an unmet need for novel treatment options remains high. After treatment with approved therapies for AML, many patients either do not achieve complete response (CR) or relapse after CR. There is no approved therapy and limited treatment options for patients with relapsed or refractory (r/r) AML. CR rates of 12% to 18% with repeated cycles of chemotherapy are reported in this patient population.**

Myelodysplastic Syndromes (MDS) are a group of bone marrow disorders in which the blood-forming cells in the bone marrow do not produce enough healthy blood cells. Some patients with MDS have too many young, immature blood-making cells in the bone marrow. The median overall survival rate of higher risk MDS patients is 0.8 to 3.0 years. There is currently no curative treatment for patients who relapse after front-line therapy or do not respond to front-line therapy. MDS can progress to AML in about one-third of patients.

*Ming Yi et al, J Hematol Oncol. 2020; 13: 72.
**Roboz et al, JCO 2014; 32: 18. Faderl et al, JCO 2012; 30: 20. Ravandi et al, Lancet 2015; 16: 9.

On October 7, 2021 Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported a clinical update of its wholly-owned, next-generation Bicycle Toxin Conjugates (BTCs), interim Phase I trial results for BT5528 and preliminary findings from the ongoing dose escalation portion of the BT8009 clinical trial (Press release, Bicycle Therapeutics, OCT 7, 2021, View Source [SID1234590937]).

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"We are pleased to provide a clinical update for two of our wholly-owned BTCs currently undergoing Phase 1 dose escalation trials in late line cancer patients," said Dominic Smethurst, MA, MBChB, MRCP, MFPM, Chief Medical Officer of Bicycle Therapeutics. "We are delighted to see preliminary anti-tumor activity in both trials and across two tumor types, as well as to report tolerability profiles that may demonstrate differentiation from antibody-based approaches."

"These data support our belief that the Bicycle platform offers a potentially differentiated approach to traditional toxin delivery. The data generated from these molecules provide a wealth of information and insights as we continue to expand the application of our technology and generate additional Bicycle- targeted therapeutics with the intention of making a meaningful difference to cancer patients," said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. "We look forward to providing additional clinical data on BT5528 and BT8009 next year, and initiating our Phase I/II study for BT7480 later this year."

BT5528, a BTC targeting EphA2, a target for which prior antibody-based approaches have been unsuccessful, has demonstrated preliminary anti-tumor activity. Bicycle has established an RP2D range and is pursuing enrollment in expansion cohorts

Preliminary signs of anti-tumor activity observed. A total of 24 patients were dosed both prior to, and after, the implementation of the EphA2 immunohistochemistry (IHC) assay, with a median of seven prior lines of therapy. Amongst these patients, preliminary anti-tumor activity was observed in urothelial and ovarian cancer patients.

A total of two BT5528 monotherapy urothelial patients were dosed. Both (100%) were observed to have tumor reductions constituting a partial response under Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The administered doses in these patients ranged from 6.5mg/m2 to 10 mg/m2 every other week.

A total of eight BT5528 monotherapy ovarian cancer patients were dosed. Of these eight, five were determined to be EphA2-positive based on the IHC assay. Anti-tumor activity was observed in four of the five (80%) patients, including one (20%) that constituted a partial response under RECIST version 1.1 criteria. The range of administered doses in these patients was 6.5- 8.5mg/m2 every other week.
Doses of BT5528 administered to date have been tolerated in the ongoing Phase I portion of the Phase I/II trial. In addition, and in contrast to the toxicities observed with MedImmune’s EphA2 antibody-drug conjugate (ADC) MEDI-547, Bicycle has observed no signs of coagulopathy to date.
Based on the Phase I results, Bicycle has established an RP2D range. BT5528 has been dosed up to 8.5mg/m2 every week and 10mg/m2 every other week. Some mild and transient neutropenia was observed at 8.5mg/m2 every week, although this did not constitute a DLT. At 10mg/m2 every other week, two DLTs were observed (Grade 3 fatigue and Grade 3 pneumonitis). The most common Grade 3 and above events were neutropenia, anemia and pneumonitis and there were two Grade 5 events: tumor lysis syndrome and renal failure caused by GI-related dehydration. Based on the totality of the findings, the RP2D is expected to be in the range of 6.5 mg/m2 to 8.5mg/m2 every other week, a dose that is believed to be within the therapeutic range based on both preclinical studies and preliminary clinical anti-tumor activity.
Bicycle to advance BT5528 in expansion cohorts. Based on the findings from the Phase I trial, Bicycle plans to initiate expansion cohorts in urothelial and ovarian cancers as well as a basket that includes head and neck, non-small cell lung, gastroesophageal and triple negative breast cancers in 2022. The trial will enroll up to 56 patients in the initial expansion cohorts, with the ability to further expand enrollment based on the results of the initial expansion cohorts.
BT8009, a Nectin-4 targeting BTC with a potentially differentiated profile as compared to a Nectin-4 targeting ADC has shown preliminary anti-tumor activity in the ongoing Phase I portion of its Phase I/II trial.

Preliminary signs of anti-tumor activity in urothelial patients observed. As of September 30, a total of 11 response evaluable urothelial cancer patients have been dosed in monotherapy cohorts of 2.5mg/m2 and 5.0mg/m2 weekly in the ongoing trial. Of these, four patients were in the 2.5mg/m2 dose cohort and seven in the 5.0mg/m2 dose cohort. Prior to enrollment, all patients had previously received at least two prior lines of therapy, with a median of two and a range of two-to-six prior therapies. A total of four patients (36%) were observed to have tumor reductions that constituted partial responses under RECIST 1.1, with a range in tumor reductions from 37% to 89% among these patients.

Four response evaluable patients were dosed at 2.5mg/m2 weekly. Among these four patients, three patients were observed to have at least stable disease, with a disease control rate of 75% and one patient (25%) was observed to have a tumor reduction of 37%, meeting the criteria of a partial response under RECIST 1.1.

Seven response evaluable patients were dosed at 5.0mg/m2 weekly. Among these seven patients, five were observed to have at least stable disease, with a disease control rate of 71% and three patients (43%) were observed to have tumor reductions meeting the criteria of a partial response under RECIST 1.1. The magnitude of tumor reductions ranged from 44% to 89%.
Dose escalation remains ongoing. At both 2.5mg/m2 weekly and 5.0mg/m2 weekly, BT8009 has been tolerated, with no DLTs observed to-date. At 5.0mg/m2 weekly, BT8009 is estimated to administer over 35% more MMAE per four-week dosing cycle compared to the antibody-based drug conjugate, enfortumab vedotin. The escalation remains ongoing, and patients are currently being enrolled in 7.5mg/m2 weekly and every other week cohorts.
BT8009 enrollment ongoing. A total of 14 clinical sites are active globally, including nine outside of the United States. Bicycle expects to have up to 21 sites active this year.
Conference Call Details

Bicycle Therapeutics will host a conference call and webcast on Thursday, October 7 at 3:00 p.m. ET to review the BT5528 trial data being presented at the AACR (Free AACR Whitepaper)-NCI-EORTC meeting and provide an update on preliminary findings from the BT8009 trial. To access the call, please dial (800) 377-9118 (domestic) or (409) 937-8920 (international) and provide the Conference ID 2287246. A live webcast of the presentation will be available on the Investors & Media section of the Bicycle website, bicycletherapeutics.com.