On November 3, 2022 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that the updated results from three studies of the company’s novel drug candidate, olverembatinib (HQP1351), have been selected for oral presentations at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Ascentage Pharma, NOV 3, 2022, View Source;ascentage-pharma-to-present-data-of-olverembatinib-hqp1351-in-three-oral-reports-including-the-first-dataset-from-the-first-us-study-at-the-ash-annual-meeting-301668292.html [SID1234623049]). This is the fifth consecutive year in which studies of olverembatinib were selected for oral presentations at the ASH (Free ASH Whitepaper) Annual Meeting, a growing recognition of the drug candidate’s promising efficacy and safety by the international hematology community. It is worth noting that in this year, five studies of Ascentage Pharma’s three drug candidates (olverembatinib, lisaftoclax, alrizomadlin), have been selected for presentations, including four oral presentations.

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It is worth noting that these results selected for oral presentations at the ASH (Free ASH Whitepaper) Annual Meeting also include the first batch of safety and efficacy data from the first US study of olverembatinib in patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). These interim results suggest that olverembatinib has promising efficacy and is well tolerated in patients with drug-resistant CML and Ph+ ALL, and has shown promising efficacy in patients who were ponatinib or asciminib resistant. Overall, these interim results signal olverembatinib’s potential as the world’s first next-generation BCR-ABL inhibitor that could overcome resistance to ponatinib or asciminib.

Additionally, data selected for the other two oral presentations include the updated results from a Phase II pivotal study of olverembatinib in patients with tyrosine kinase inhibitor (TKI)-resistant CML harboring the T315 mutation and the five-year follow-up data from a Phase I study in Chinese patients with TKI-resistant CML. These results further validate the promising safety and efficacy of olverembatinib.

The ASH (Free ASH Whitepaper) Annual Meeting is one of the largest gatherings of the international hematology field, bringing together the latest and most cutting-edge scientific and clinical research in hematology. The 64th ASH (Free ASH Whitepaper) Annual Meeting will take place on December 11-14, 2022, both online and in-person in New Orleans, the United States.

Developed by Ascentage Pharma, olverembatinib is a potential best-in-class novel drug that has been designated a Major New Drug Project by China’s Ministry of Science and Technology. As the first approved third-generation BCR-ABL inhibitor in China and the second in any country globally, olverembatinib is recommended by both the Guidelines of the Chinese Society of Clinical Oncology (CSCO) and the China Anti-Cancer Association’s (CACA) Guidelines for the Holistic Integrative Management of Cancers, for the treatment of patients with TKI-resistant CML harboring the T315I mutation (while the CACA Guidelines also recommend olverembatinib for the treatment of patients with CML intolerant/resistant to at least two TKIs).

Globally, despite the clinical adoption of other TKI, patients with CML still have enormous unmet medical needs due to the limited accessibility as well as adverse events, resulting in the strong interest in the clinical progress with olverembatinib from the global hematology community in recent years. At present, olverembatinib is being evaluated in a Phase Ib study in the US for the treatment of drug-resistant CML. Furthermore, olverembatinib has been granted one Fast Track designation and four Orphan Drug designations by the US Food and Drug Administration (FDA), and one Orphan Drug designation by the European Medicines Agency (EMA).

To address the unmet medical needs in patients with CML, Ascentage Pharma is pressing ahead with the global clinical development of olverembatinib and advancing the drug towards approvals in more countries. Driven by a sense of urgency to facilitate the early access by patients with malignancies that currently lack treatment options, Ascentage Pharma and Tanner Pharma Group, a global pharmaceutical services provider of specialty access solutions, jointly launched an innovative Named Patient Program (NPP) for olverembatinib in July 2022. This collaboration will allow access to olverembatinib on a named patient basis in over 140 countries and regions where the drug is not yet commercially accessible, in a manner that is reliable, responsible, ethical and in accordance with all country-specific regulatory requirements.

"For five consecutive years, results of olverembatinib have been selected for oral presentations at the ASH (Free ASH Whitepaper) Annual Meeting, thus setting a new record signifying the growing recognition from the international hematology community," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "The first US data of olverembatinib showed the drug’s potential as the world’s first BCR-ABL inhibitor that can overcome the resistance to ponatinib and asciminib. We are encouraged by these results because they further validate that olverembatinib can potentially bring a long-awaited change to the treatment landscape in CML by effectively addressing the unmet needs of patients with CML globally. Moving forward, we will continue to accelerate the global clinical development of olverembatinib to fast track the drug towards approvals in overseas markets and more indications in China, with the hope of benefiting more patients around the world."

"We have also launched a Global Named Patient Program in 140 countries where the drug is not commercially available. The program makes Olverembatinib available to patients at the treating physician’s decision in these countries", said Prof Dajun Yang, Chairman and CEO of Ascentage Pharma.

Drug Candidate

Abstract Title

Abstract#

Format

Olverembatinib

Olverembatinib (HQP1351) Overcomes
Ponatinib Resistance in Patients with Heavily
Pretreated/Refractory Chronic Myeloid
Leukemia (CML) and Philadelphia
Chromosome-Positive Acute Lymphoblastic
Leukemia (Ph+ ALL)

162387

Oral
Presentation

口头报告

Updated Results of Pivotal Phase 2 Trials of
Olverembatinib (HQP1351) in Patients (Pts)
with Tyrosine Kinase Inhibitor (TKI)-Resistant
Chronic- and Accelerated-Phase Chronic
Myeloid Leukemia (CML-CP and CML-AP) with
T315I Mutation

170698

Oral
Presentation

A Five-Year Follow-up on Safety and Efficacy of
Olverembatinib (HQP1351), a Novel Third-
Generation BCR-ABL Tyrosine Kinase Inhibitor
(TKI), in Patients with TKI-Resistant Chronic
Myeloid Leukemia (CML) in China

170868

Oral
Presentation

APG-2575

Lisaftoclax

Lisaftoclax (APG-2575) Safety and Activity As
Monotherapy or Combined with Acalabrutinib
or Rituximab in Patients (pts) with Treatment-
Naïve, Relapsed or Refractory Chronic
Lymphocytic Leukemia/Small Lymphocytic
Lymphoma (R/R CLL/SLL): Initial Data from a
Phase 2 Global Study

160386

Oral
Presentation

(APG-115)

Alrizomadlin

MDM2-p53 Inhibitor Alrizomadlin (APG-115)
Enhances Antitumor Activity of Pomalidomide
in Multiple Myeloma (MM)

162666

Poster
Presentation

The three abstracts of olverembatinib to be reported in oral presentations at this year’s ASH (Free ASH Whitepaper) Annual Meeting are as follows (for details of the oral presentation on lisaftoclax, please refer to a parallel press release):

Olverembatinib (HQP1351) Overcomes Ponatinib Resistance in Patients with Heavily Pretreated/Refractory Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL)

Format: Oral Presentation
Abstract: 162387
Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Novel Agents
Time: Saturday, December 10, 2022, 10:15 AM, Eastern Time / Saturday, December 10, 2022, 11:15 PM, Beijing Time
Highlights:
Olverembatinib is a novel third-generation BCR-ABL1 TKI with antitumor activity against CML and Ph+ ALL and a favorable safety profile.
This multicenter, open-label, randomized trial is the first to report on the safety, efficacy, and pharmacokinetics (PK) of olverembatinib in patients with CML and Ph+ ALL outside China, who were intolerant or resistant to at least 2 BCR-ABL1 inhibitors, including ponatinib and asciminib, except for those whose disease harbors the T315I mutation, for whom the number of prior lines of therapy is not limited. Study participants were randomized in a ratio of 3:3:2 to receive olverembatinib 30, 40, or 50 mg QOD in 28-day cycles.
A total of 30 patients have been enrolled, including 23 with CML-CP, 4 with CML-AP, 2 with blast-phase CML (CML-BP), and 1 with Ph+ ALL. The median treatment duration was 4.8 (range, 0.03-21.29) months and the median interval from CML/Ph+ ALL diagnosis to receiving the olverembatinib treatment was 7.0 (range, 1.5-24.0) years. Half (15/30) of patients were men, and the median age was 47.0 (range, 21.0-74.0). In all, 1 (3.3%), 7 (23.3%), 8 (26.7%), and 9 (30.0%) patients received 2, 3, 4, and ≥ 5 prior TKIs, respectively. A total of 21 (70.0%) patients were pretreated with the third-generation TKI ponatinib, including 17 (81.0%) with resistance and 4 (19.0%) with intolerance; a total of 5 (16.7%) were pretreated with asciminib; 12 (40.0%) had T315I mutations; and 13 (43.3%) had hypertension.
Safety: Olverembatinib was well tolerated. 22 (73.3%) patients experienced treatment related adverse events (TRAEs) of any grade, the incidence of which tended to be dose-dependent. Most of the nonhematologic TRAEs were grade 1/2. Common grade 3/4 nonhematologic TRAEs included thrombocytopenia (7/30; 23.3%), neutropenia (5/30; 16.7%), and decreased leukocyte counts (4/30; 13.3%). Of all 30 patients, 11(36.7%) experienced serious adverse events (SAEs), of which 6 (20%) were considered olverembatinib-related and 1 (3.3%) led to treatment discontinuation. 1 patient with CML-AP from the 50 mg dose cohort died of progressive disease (PD).
Preliminary efficacy: Olverembatinib conferred potent antileukemic activity in patients with CML and Ph+ ALL. Of 21 efficacy-evaluable patients, 17 were evaluable for cytogenetic response, of whom 10 (58.8%) had a complete cytogenetic response (CCyR); 9/21 (42.9%) patients had a major molecular response (MMR). Olverembatinib was effective in patients with either the T315I-mutant (62.5%, CCyR; 50%, MMR) or T315I un-mutant (55.6%, CCyR; 38.5%, MMR), and its effectiveness was not compromised by prior use of ponatinib or asciminib. Among patients with ponatinib-resistant disease, 5/9 (55.6%) experienced CCyR and 6/11 (54.5%) experienced MMR. 4 of 5 patients pretreated with asciminib showed response. PK analysis indicated a dose-proportional increase in olverembatinib plasma exposure from 30 to 50 mg QOD and comparable plasma exposures between Chinese and US CML populations.
Conclusions: Olverembatinib monotherapy is efficacious and well tolerated in patients with TKI-refractory CML and Ph+ ALL. Even in patients with CML who were ponatinib or asciminib resistant, or who had T315I mutations, olverembatinib also showed strong efficacy.
Updated Results of Pivotal Phase 2 Trials of Olverembatinib (HQP1351) in Patients (Pts) with Tyrosine Kinase Inhibitor (TKI) -Resistant Chronic- and Accelerated-Phase Chronic Myeloid Leukemia (CML-CP and CML-AP) with T315I Mutation

Format: Oral Presentation
Abstract: 170698
Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Novel Agents
Time: Saturday, December 10, 2022, 10:30 AM, Eastern Time / Saturday, December 10, 2022, 11:30 PM, Beijing Time
Highlights:
The T315I mutation can confer a high degree of resistance to many first- and second-generation TKIs. Olverembatinib is a novel, orally active, third-generation BCR-ABL1 TKI. These Phase II pivotal trials, HQP1351-CC-201 and HQP1351-CC-202, conducted based on favorable Phase I trial results, showed that olverembatinib was efficacious and well tolerated in patients with TKI-resistant CML-CP and CML-AP with the BCR-ABL1T315I mutation.
The HQP1351-CC-201 Study (in patients with CML-CP)
As of the cutoff date of April 30, 2022, 41 patients were enrolled, of whom 21 (51.2%) were male, with a median age of 47 (range, 22-70) years. The median interval from CML diagnosis to first olverembatinib dose was 5.31 (range, 0.6-23.2) years, and 32 (78.1%) patients had received ≥ 2 prior TKIs. The median treatment duration was 32.7 (range, 3.1-36.7) months.

Preliminary efficacy: 100% of patients achieved complete hematologic response (CHR) (31/31, 10 others had CHR at baseline), 34/41 (82.9%) had a major cytogenetic response (MCyR), 29/41 (70.7%) CCyR, and 24/41 (58.5%) MMR. Median time to CHR was 1 (95% CI: 1.0-1.9) month, median time to MCyR was 2.8 (95% CI: 2.8-5.6) months, and median time to MMR was 6.5 (95% CI: 2.8 to not reached [NR]) months. At 36 months, the progression-free survival (PFS) rate was 86.3% (95% CI: 70.2%-94.1%) and the overall survival (OS) rate was 95.1% (95% CI: 81.9%-98.8%). A total of 5 patients withdrew because of PD, 4 intolerances, 3 consent withdrawals, and 2 for other reasons.

Safety: Frequent TRAEs (all grades; grade 3-4; SAEs) included thrombocytopenia (70.7%; 48.8%; 7.3%), anemia (70.7%; 31.7%; 2.4%), leukopenia (51.2%; 14.6%; 0), and neutropenia (41.4%; 21.9%; 0). Common nonhematologic TRAEs (all grades; grade 3-4) included skin pigmentation (56.1%; 0%) and elevations in creatine kinase (56.1%; 19.5%), alanine transaminase (ALT, 43.9%; 2.4%) and aspartate aminotransferase (AST, 36.6%; 0) levels.

The HQP-1351-CC-202 Study (in patients with CML-AP)
As of the cutoff date of April 30,2022, 23 patients were enrolled, of whom 18 (78.3%) were male, with a median age of 41 (range, 21-74) years. The median interval from CML diagnosis to first olverembatinib dose was 4.96 (range, 0.4-10.2) years, and 19 (82.6%) patients had received ≥ 2 prior TKIs. The median treatment duration was 19.7 (range, 1.4-36.4) months.

Preliminary efficacy: A total of 18 (78.3%) patients experienced a major hematologic response (MaHR) (73.9% CHR and 4.4% no evidence of leukemia [NEL]); 12 (52.2%) MCyR; 12 (52.2%) CCyR; and 11 (47.8%) MMR. The median time to MaHR was 2.8 (95% CI: 1.0-4.7) months, the median time to MCyR was 5.6 (95% CI: 2.00-NR) months, and the median time to MMR was 13.1 (95% CI: 5.6-22.4) months. At 36 months, the PFS rate was 57.1% (95% CI: 33.3%-75.1%) and the OS rate was 69.6% (95% CI: 46.6%-84.2%). 6 patients withdrew because of PD, 4 because of intolerances, and 1 for other reasons; two patients died.

Safety: Common TRAEs (all grades; grade 3-4; SAEs) included thrombocytopenia (78.3%; 56.5%; 17.4%), anemia (69.6%; 34.8%; 13.0%), leukopenia (56.5%; 30.4%; 0), and neutropenia (26.1%; 26.1%; 0). Common nonhematologic AEs included skin pigmentation (69.6%), hypocalcemia (52.2%), proteinuria (56.5%), hypertriglyceridemia (60.9%), hyperphosphatemia (47.8%), hyperuricemia (26.1%), and arthralgia (34.8%), of which most were grade 1-2.

Conclusions: Olverembatinib was efficacious and well tolerated in patients with TKI-resistant CML-CP and CML-AP with the BCR-ABL1T315I mutation. Based on the results of these pivotal trials, the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) granted conditional approval for olverembatinib in November 2021.
A Five-Year Follow-up on Safety and Efficacy of Olverembatinib (HQP1351), a Novel Third-Generation BCR-ABL Tyrosine Kinase Inhibitor (TKI), in Patients with TKI-Resistant Chronic Myeloid Leukemia (CML) in China

Format: Oral Presentation
Abstract: 170868
Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Novel Agents
Time: Saturday, December 10, 2022, 10:00 AM, Eastern Time / Saturday, December 10, 2022, 11:00 PM, Beijing Time
Highlights
This open-label, multi-center Phase I study assessed a 5-year follow-up on the safety and efficacy of olverembatinib in adult patients with CML-CP or CML-AP resistant or intolerant to first- or second-generation TKIs. Patients evaluated in the study were orally administered olverembatinib QOD in 28-day cycles in 11 dose cohorts ranging from 1 to 60 mg.
From October 26, 2016, to April 30, 2022 (data cutoff date), 101 patients with CML-CP (n = 86) and CML-AP (n = 15) were enrolled and treated with olverembatinib. The median treatment duration was 44.7 (1.2-63.1) months. 71 (70.3%) patients were male, with a median age of 40 (range, 20-64) years and a median interval from diagnosis to initial olverembatinib treatment of 6.0 (range, 0.3-15.2) years. A total of 84 (83.2%) patients received ≥2 lines of TKI therapy, and 63 (62.4%) had disease harboring the T315I mutation. At baseline, compound mutations were detected in 12 (11.9%) patients, of whom 8 (66.7%) harbored the BCR-ABL1T315I mutation. A total of 20 (19.9%) patients had 2 (n = 13) or ≥ 3 (n = 7) mutations. As of the data cutoff date, 72 (71.3%) patients continued treatment and 28 (21 with CML-CP and 7 with CML-AP) discontinued because of disease progression, intolerance, or other reasons. The cumulative median drug exposure dose was 20,175 (range, 660-34,395) mg. Of the 101 patients, 79 (78.2%) were treated > 3 years, 21 (20.8%) > 4 years, and 3 (3.0%) > 5 years.
Preliminary efficacy: Of the evaluable patients with CML-CP, 100% experienced CHR, 80% MCyR, 71.3% CCyR, and 55.3% MMR; Of the evaluable patients with CML-AP, 85.7% had CHR and 40% each for MCyR, CCyR, and MMR; Of evaluable patients with the T315I mutation, 100% of those with CML-CP experienced CHR, 83.7% MCyR, and 73.1% MMR and 80.0% with CML-AP had CHR and 54.5% each for MCyR and MMR. PFS at 48 months was 85.6% (95% CI: 70.6%-93.3%) in patients with CML-CP and 50.0% (95% CI: 22.9%-72.2%) in patients with CML-AP; In the 12 patients with compound mutations, next-generation sequencing confirmed that 7 (58.0%) experienced MMR and 3 (25.0%) MR4.5. At the last follow-up, 3 patients had progressed to CML-AP or CML-BP and died, and 7 remained on olverembatinib. One patient had an MMR and 2 each CHR, CCyR, or MR4.5.
Safety: Most TRAEs were grade 1-2. The most frequent nonhematologic AE was, primarily, grade 1-2 skin hyperpigmentation (85.1%). Grade ≥ 3 nonhematologic AEs included hypertriglyceridemia (10.9%), pyrexia (6.9%), and proteinuria (6.9%). The common hematologic TRAE was thrombocytopenia, which was observed in 79 (78.2%) patients, including 52 (51.5% of total population) with grade ≥ 3 and 7 (6.9%) with SAEs. Leukopenia was grade ≥ 3 in 21 (20.8%) patients but not serious, while anemia was grade ≥ 3 in 17 (16.8%) and serious in 4 (4.0%).
Conclusions: The 5-year follow-up results of this first-in-human trial show durable responses and good tolerance of olverembatinib in heavily pretreated patients with CML.

On November 3, 2022 Exact Sciences Corp. (Nasdaq: EXAS), a leading provider of cancer screening and diagnostic tests, reported that the company generated revenue of $523 million for the third quarter ended September 30, 2022, compared to $456 million for the same period of 2021 (Press release, Exact Sciences, NOV 3, 2022, View Source [SID1234623048]).

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"Exact Sciences third quarter results demonstrate the strength of our business and the unique platform this team has built to engage patients and physicians," said Kevin Conroy, chairman and CEO. "As we quickly approach profitability and make more innovative cancer tests available to patients, our Cologuard and Oncotype DX tests, best-in-class customer experience, broad sales and marketing reach, and powerful lab and technology foundation will continue to gain momentum and help achieve our vision to eradicate cancer."

Third quarter 2022 financial results

For the three-month period ended September 30, 2022, as compared to the same period of 2021 (where applicable):

Total revenue was $523.1 million, an increase of 15 percent, or 20 percent excluding COVID-19 testing
Screening revenue was $360.8 million, an increase of 29 percent, or 25 percent excluding the PreventionGenetics acquisition
Precision Oncology revenue was $151.4 million, an increase of 4 percent, or 9 percent excluding the Oncotype DX Genomic Prostate Score test, which was divested on August 2, 2022, and the impact of foreign currency exchange rates
COVID-19 testing revenue was $10.9 million, a decrease of 64 percent
Gross margin including amortization of acquired intangible assets was 68 percent, and non-GAAP gross margin excluding amortization of acquired intangible assets was 72 percent
EBITDA was $(98.1) million and adjusted EBITDA was $(13.0) million
Cash, cash equivalents, and marketable securities were $669.1 million at the end of the quarter
Screening includes laboratory service revenue from Cologuard tests, PreventionGenetics, and immaterial revenue from Biomatrica and Oncoguard Liver products. Precision Oncology includes laboratory service revenue from global Oncotype products and therapy selection products, including OncomapTM and OncomapTM ExTra, formerly known as Oncotype MapTM and GEM ExTra, respectively.

2022 outlook

The company anticipates revenue of $2,025-$2,042 million during 2022, assuming:

Screening revenue of $1,375-$1,382 million, including $40-$42 million from PreventionGenetics,
Precision Oncology revenue of $595-$600 million, and
COVID-19 testing revenue of $55-$60 million.
Revenue guidance has been raised from the previously expected range of $1,980-$2,022 million, which assumed:

Screening revenue of $1,350-$1,372 million, including $40-$42 million from PreventionGenetics,
Precision Oncology revenue of $580-$590 million, and
COVID-19 testing revenue of $50-$60 million.
Non-GAAP disclosure
In addition to the company’s financial results determined in accordance with U.S. GAAP, the company provides non-GAAP measures that it determines to be useful in evaluating its operating performance. The company presents EBITDA, adjusted EBITDA, as well as non-GAAP gross margin and non-GAAP gross profit. EBITDA and adjusted EBITDA consist of net loss after adjustment for those items shown in the table below. The company defines non-GAAP gross profit and non-GAAP gross margin as GAAP gross profit and GAAP gross margin, respectively, excluding amortization of acquired intangible assets. The amortization of acquisition-related intangible assets used in the calculation of non-GAAP gross profit and non-GAAP gross margin pertain only to the amortization associated with developed technology acquired and recorded through purchase accounting transactions. The amortization of these intangible assets will recur in future periods until such intangible assets have been fully amortized. The company believes that these non-GAAP measures are useful in evaluating the company’s operating performance. The company uses this non-GAAP financial information to evaluate ongoing operations and for internal planning and forecasting purposes. Non-GAAP financial information, when taken collectively, may be helpful to investors because it provides consistency and comparability with past financial performance. However, non-GAAP financial information is presented for supplemental information purposes only, has limitations as an analytical tool and should not be considered in isolation or as a substitute for financial information presented in accordance with U.S. GAAP. For example, non-GAAP gross margin and non-GAAP gross profit exclude the amortization of acquired intangible assets although such measures include the revenue associated with the acquisitions. Additionally, adjusted EBITDA excludes a number of expense items that are included in net loss. As a result, positive adjusted EBITDA may be achieved while a significant net loss persists. For a reconciliation of these non-GAAP measures to GAAP, see below "EBITDA and Adjusted EBITDA Reconciliations" and "Non-GAAP Gross Profit and Non-GAAP Gross Margin Reconciliations." Information reconciling forward-looking non-GAAP measures to U.S. GAAP measures is not available without unreasonable effort.

Third quarter conference call & webcast
Company management will host a conference call and webcast on Thursday, November 3, 2022, at 5 p.m. ET to discuss third quarter 2022 results. The webcast will be available at exactsciences.com. Domestic callers should dial 888-330-2384 and international callers should dial +1-240-789-2701. The access code for both domestic and international callers is 4437608.

An archive of the webcast will be available at exactsciences.com. A replay of the conference call will be available by calling 800-770-2030 domestically or +1-647-362-9199 internationally. The access code for the replay of the call is 4437608. The webcast, conference call, and replay are open to all interested parties.

About Cologuard
The Cologuard test was approved by the FDA in August 2014, and results from Exact Sciences’ prospective 90-site, point-in-time, 10,000-patient pivotal trial were published in the New England Journal of Medicine in March 2014. The Cologuard test is included in the American Cancer Society’s (2018) colorectal cancer screening guidelines and the recommendations of the U.S. Preventive Services Task Force (2021) and National Comprehensive Cancer Network (2016). The Cologuard test is indicated to screen adults 45 years of age and older who are at average risk for colorectal cancer by detecting certain DNA markers and blood in the stool. Do not use the Cologuard test if you have had precancer, have inflammatory bowel disease and certain hereditary syndromes, or have a personal or family history of colorectal cancer. The Cologuard test is not a replacement for colonoscopy in high risk patients. The Cologuard test performance in adults ages 45-49 is estimated based on a large clinical study of patients 50 and older. The Cologuard test performance in repeat testing has not been evaluated.

The Cologuard test result should be interpreted with caution. A positive test result does not confirm the presence of cancer. Patients with a positive test result should be referred for diagnostic colonoscopy. A negative test result does not confirm the absence of cancer. Patients with a negative test result should discuss with their doctor when they need to be tested again. Medicare and most major insurers cover the Cologuard test. For more information about the Cologuard test, visit cologuard.com. Rx only.

On November 3, 2022 Illumina, Inc. (Nasdaq: ILMN) reported its financial results for the third quarter of fiscal year 2022, which include consolidated financial results for GRAIL (Press release, Illumina, NOV 3, 2022, View Source [SID1234623047]).

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"Our third-quarter results were in line with our expectations, with traction across our portfolio offset by challenging macroeconomic dynamics that we expect will continue into 2023," said Francis deSouza, Chief Executive Officer. "Customer response to our latest innovations has been very positive; we already have 50 NovaSeq X orders globally. As we close out 2022 and look toward 2023, we are focused on helping customers navigate the current environment and delivering these technologies to help customers reimagine what’s possible with genomics."

(a) See the tables included in "Results of Operations – Non-GAAP" section below for reconciliations of these GAAP and non-GAAP financial measures.

(b) Consolidated financial results for GRAIL are included in Q3 2022 and in Q3 2021 for the period after the acquisition on August 18, 2021.

(c) During the third quarter of 2022, the company recognized $3.91 billion in goodwill impairment related to the GRAIL segment, primarily due to the negative impact of current capital market conditions and higher discount rates, including a standalone risk premium, on the fair value calculation of the GRAIL segment.

Capital expenditures for free cash flow purposes were $67 million during the third quarter of 2022. Cash flow used in operations was $(52) million, which included a one-time payment related to the litigation settlement with BGI, compared to $(272) million in the prior year period, which included transaction expenses related to the GRAIL acquisition on August 18, 2021. Free cash flow (cash flow used in operations less capital expenditures) was $(119) million for the quarter, compared to $(324) million in the prior year. Depreciation and amortization expenses were $103 million during the third quarter of 2022. At the close of the quarter, the company held $1,041 million in cash, cash equivalents and short-term investments, compared to $1,339 million as of January 2, 2022.

Third quarter segment results
Following the acquisition of GRAIL on August 18, 2021, Illumina has two reportable segments, Core Illumina and GRAIL. GRAIL financial results are reflected for the period after the acquisition.

Key announcements by Illumina since Illumina’s last earnings release

Announced multiple breakthrough sequencing innovations at the inaugural Illumina Genomics Forum, including:
NovaSeqX Series (NovaSeq X and NovaSeq X Plus), available in Q1 2023, enabling the highest levels of accuracy at immense scale, with the power to sequence more than 20,000 genomes per year
NovaSeq 6000Dx, available now as the first FDA-registered and CE-marked in vitro diagnostic (IVD) high-throughput sequencer
Illumina Complete Long-Reads, available in 2023, delivering a complete and accurate representation of the genome at the single molecule on both existing and new sequencing platforms
XLEAP-SBS Chemistry on the NextSeq 1000/2000 available in 2024
Partnered with GenoScreen to expand global access to genomic testing for multi-drug resistant tuberculosis (TB) by combining Illumina sequencing products and the GenoScreen Deeplex Myc-TB assay, a targeted next-generation sequencing (NGS) based test for rapid and extensive detection of anti-TB drug resistance
Deepened strategic collaboration with AstraZeneca to accelerate drug target discovery based on human omics insights by combining strengths in artificial intelligence based genome interpretation and genomic analysis along with industry expertise
Opened the first manufacturing site in China to enable localized production for NGS instruments and consumables
Partnered with Minderoo Foundation to accelerate scientific understanding of marine systems using the power of high-throughput sequencing
Introduced new research test for genitourinary pathogen and antimicrobial resistance identification that applies metagenomics to detect and quantify pathogens
Hosted both Investor Day and ESG Investor Event in October with presentations from management on company strategic direction, key business areas, innovation roadmap developments and ESG strategy
A full list of recent Illumina announcements can be found in the company’s News Center.

Key announcements by GRAIL since Illumina’s last earnings release

Expanded offering of Galleri across the U.S. through partnerships with Carrum Health, to include Galleri as part of its comprehensive cancer care to self-insured employers, and with Henry Ford Health, the first healthcare provider in Michigan to offer Galleri
Announced final results from the PATHFINDER multi-cancer early detection screening study at ESMO (Free ESMO Whitepaper) Congress 2022, demonstrating that adding multi-cancer early detection screening to standard care screening more than doubled the number of cancers detected
Partnered with John Hancock, the first life insurance carrier to offer access to Galleri to customers
A full list of recent GRAIL announcements can be found in GRAIL’s Newsroom.

Financial outlook and guidance
The non-GAAP financial guidance discussed below reflects certain pro forma adjustments to assist in analyzing and assessing our core operational performance, including our Core Illumina and GRAIL segments. Please see our Reconciliation of Consolidated Non-GAAP Financial Guidance included in this release for a reconciliation of these GAAP and non-GAAP financial measures.

For fiscal 2022, the company now expects consolidated revenue to be flat to 1% higher compared to fiscal year 2021. We now expect GAAP diluted loss per share of $(26.56) to $(26.41) and non-GAAP diluted earnings per share of $2.35 to $2.50. The GAAP and non-GAAP diluted (loss) earnings per share guidance ranges continue to assume that the R&D expense capitalization requirement implemented by the Tax Cuts and Jobs Act of 2017 will be repealed in the fourth quarter of 2022. If the R&D expense capitalization requirement is not repealed in 2022, the company’s tax expense will be negatively impacted.

Core Illumina revenue growth is now expected to be approximately flat from fiscal year 2021. GRAIL revenue is now expected to be in the range of $55 million to $65 million.

Conference call information
The conference call will begin at 2 p.m. Pacific Time (5 p.m. Eastern Time) on Thursday, November 3, 2022. Interested parties may access the live teleconference through the Investor Info section of Illumina’s website under the "Company" tab at www.illumina.com. Alternatively, individuals can access the call by dialing 866.409.1555 or +1.313.209.4906 outside North America, both using conference ID 7679670. To ensure timely connection, please dial in at least ten minutes before the scheduled start of the call.

A replay of the conference call will be posted on Illumina’s website after the event and will be available for at least 30 days following.

On November 3, 2022 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported the closing of its previously announced upsized underwritten public offering of 7,895,522 shares of Class A common stock, which includes 1,029,850 shares of Class A common stock sold pursuant to the exercise in full by the underwriters of their option to purchase additional shares, at a price to the public of $33.50 per share (Press release, Nuvalent, NOV 3, 2022, View Source [SID1234623046]). The gross proceeds of the offering were approximately $264.5 million, before deducting underwriting discounts and commissions and other offering expenses. All shares in the offering were offered by Nuvalent.

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J.P. Morgan, Cowen, Piper Sandler and BMO Capital Markets acted as joint book-running managers for the offering.

The shares were offered by Nuvalent pursuant to a shelf registration statement that was filed with the Securities and Exchange Commission ("SEC") on August 10, 2022, and declared effective by the SEC on August 16, 2022. This offering was made only by means of a prospectus and prospectus supplement that form a part of the registration statement. A final prospectus supplement relating to and describing the terms of the offering has been filed with the SEC and may be obtained for free by visiting the SEC’s website at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus can be obtained from: J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone (866) 803-9204 or by email at [email protected]; Cowen and Company, LLC c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY, 11717, Attn: Prospectus Department, by email at [email protected] or by telephone at (833) 297-2926; Piper Sandler & Co., 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, Attention: Prospectus Department, by telephone at (800) 747-3924, or by email at [email protected]; and BMO Capital Markets Corp., Attn: Equity Syndicate Department, 151 W 42nd Street, 32nd Floor, New York, NY 10036, by telephone at (800) 414-3627, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On November 3, 2022 Akeso, Biopharma (9926. HK) ("Akeso") reported the patient enrollment completion for the Phase III clinical trial of Ivonescimab (PD-1/VEGF bi-specific antibody, AK112) combined with chemotherapy for the treatment of EGFR-mutant locally advanced or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) who have failed to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment (Press release, Akeso Biopharma, NOV 3, 2022, View Source [SID1234623045]).

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This trial is a randomized, double-blind, multi-center Phase III clinical trial, which started patient enrollment in end of January 2022, and it has enrolled 320 participants as of the date of this press release. The primary endpoint of the trial is progression-free survival (PFS) assessed by IRRC. This therapy was granted Breakthrough Therapy Designation by the Center for Drug Evaluation, National Medical Products Administration (CDE, NMPA) lately in October 2022.

Lung cancer is a malignant tumor with high incidence and high mortality rates worldwide. The incidences of lung cancer around the world and in China have exceeded 2.2 million and 810 thousand respectively in 2020. Non-small cell lung cancer (NSCLC) patients account for 85% of total lung cancer patients, and about 70% of NSCLC patients are diagnosed at advanced stages. In China, nsq-NSCLC accounts for 70% of NSCLC, and about 40%-50% of nsq-NSCLC patients have EGFR mutation.

Immunotherapy plus anti-angiogenesis therapy has proved its combination advantages in previous studies worldwide. Lung cancer is one of the mainstream exploration areas of this therapy. AK112 could simultaneously block PD-1 and VEGF targets and has demonstrated favourable safety profile and promising anti-tumor efficacy in ongoing studies conducted by Akeso. AK112 in combination with chemotherapy is expected to provide a novel and effective therapy for the treatment of EGFR-mutated locally advanced or metastatic nsqNSCLC patients who have failed to EGFR-TKI treatment.

ABOUT IVONESCIMAB (PD-1/VEGF BI-SPECIFIC ANTIBODY, AK112)

Ivonescimab is a first-in-class and the first to enter phase III clinical trial PD-1/VEGF bi-specific antibody independently developed by Akeso. Engineered with our unique Tetrabody technology, Ivonescimab blocks PD-1 binding to PD-L1 and PD-L2, and blocks VEGF binding to VEGF receptors. PD-1 antibody combined with VEGF blocking agents have shown robust efficacy in various tumor types (including renal cell carcinoma, non-small cell lung cancer and hepatocellular carcinoma). In view of the co-expression of VEGF and PD-1 in the tumor microenvironment, Ivonescimab, as a single agent to block these two targets, may block these two pathways more effectively and enhance the antitumor activity, as compared to combination therapy.

Currently, Akeso is conducting a phase III clinical trial of AK112 monotherapy versus Pembrolizumab monotherapy as the first-line treatment for NSCLC patients with positive PD-L1 expression. In addition, a phase III clinical trial of AK112 plus chemotherapy versus chemotherapy in EGFR mutated advanced non-squamous NSCLC that failed in prior EGFR-TKI therapy is ongoing. AK112 has been investigated in multiple clinical trials for various stages treatment of indications including non-small cell lung cancer and small cell lung cancer.