On June 18, 2021 Guardant Health reported that STUDY SHOWS GUARDANT REVEAL BLOOD-ONLY LIQUID BIOPSY TEST PREDICTS RISK FOR COLORECTAL CANCER RECURRENCE WITH INDUSTRY-LEADING SENSITIVITY (Press release, Guardant Health, JUN 18, 2021, View Source [SID1234584169]).

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For patients with early-stage colorectal cancer (CRC), the presence of circulating tumor DNA (ctDNA) or minimal residual disease (MRD) after curative intent treatment is becoming an important prognostic biomarker for cancer recurrence, and can also be used to evaluate the potential need for adjuvant treatment in post-surgical patients. Until recently, tests developed to detect MRD required tumor tissue to gain the necessary genomic information needed to accurately identify high-risk patients. A new study led by Massachusetts General Hospital Cancer Center and published in Clinical Cancer Research demonstrates that Guardant Reveal, the first blood-only liquid biopsy to identify MRD, identifies those patients most likely to recur, with industry-leading sensitivity, without the need for tumor tissue. 1,2

The single-center, prospective study evaluated the effectiveness of the Guardant Reveal liquid biopsy test to detect MRD in patients with stage I-IV colorectal cancer after curative intent therapy. Blood draws were taken one month after completion of definitive treatment, either surgery or adjuvant therapy, and at various surveillance or monitoring timepoints. Blood samples were analyzed using the Guardant Reveal test, which integrates both cancer-specific epigenomic signatures and genomic alterations, unlike standard MRD tests which analyze only genomic alterations.

In the primary landmark analysis (n=84), blood samples were taken from the curative intent patient population one month (median 31.5 days) after completion of definitive treatment. In the subset of patients with at least one year of clinical follow-up, all patients with detectable ctDNA recurred (100% PPV). Guardant Reveal test sensitivity and specificity were 55.6% and 100% respectively for this single timepoint. By incorporating longitudinal surveillance samples, sensitivity improved to 91%. Integrating epigenomic signatures increased test sensitivity by 36% versus using genomic alterations alone. Additionally, CEA tests, the traditional biomarker for colorectal cancer, did not predict recurrence in this patient cohort.

"The integration of cancer-specific epigenomic and genomic signatures allows Guardant Reveal to detect minimal residual disease in early-stage colorectal cancers with industry-leading performance and without the need for tumor tissue," said AmirAli Talasaz, Guardant Health president. "We believe that Guardant Reveal can be a powerful decision-making tool for oncologists managing patients with early-stage colorectal cancer. In addition, our blood-only approach offers a more streamlined workflow and faster turnaround time for clinical decision making."

"By detecting minimal residual disease after curative intent treatment, we can have a better understanding of which patients are at high-risk for recurrence and perhaps tailor additional therapy," said Aparna Parikh, MD, MPH, Gastrointestinal Oncologist at Massachusetts General Hospital and Assistant Professor of Medicine, Harvard Medical School. "This study demonstrates that the incorporation of epigenomic signatures with genomic alterations allows for Guardant Reveal to have high sensitivity and specificity, but without the need for tumor tissue."

Tissue-dependent MRD tests have previously reported sensitivities of 40%-50% with a single post-surgical blood draw. 1,3 When looking only at the subset of patients with stage II or III CRC in this study, Guardant Reveal had a sensitivity of 63% and a specificity of 100% for recurrence. These data show that Guardant Reveal can detect minimal residual disease from a simple blood draw. In addition, the sensitivity of the test increases with additional longitudinal blood draws, allowing for earlier detection of recurrence in the patient surveillance setting compared with standard imaging methods.

The Guardant Reveal test achieves industry-leading sensitivity (91%) 2 for detecting ctDNA by simultaneously interrogating genomic and epigenomic alterations. The test accurately identifies genomic alterations down to allele frequencies of 0.01% and effectively filters out biological noise sources such as mutations caused by clonal hematopoiesis. The incorporation of biologically relevant epigenomic signatures is essential to increasing test sensitivity in the post curative intent and surveillance patient populations.

The publication titled, "Minimal Residual Disease Detection using a Plasma-Only Circulating Tumor DNA Assay in Colorectal Cancer Patients" can be found here

On June 18, 2021 ADC Therapeutics SA (NYSE:ADCT), a commercial-stage biotechnology company leading the development of novel antibody drug conjugates (ADCs) to treat hematological malignancies and solid tumors, reported that posters on four ZYNLONTA (loncastuximab tesirine-lpyl) clinical trials were presented at the 16th Annual International Conference on Malignant Lymphoma (ICML) (Press release, ADC Therapeutics, JUN 18, 2021, View Source [SID1234584168]).

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"The updated results from our pivotal LOTIS-2 clinical trial presented at ICML continue to reinforce the efficacy across difficult-to-treat subgroups and sustained duration of response of commercially-available ZYNLONTA as a single agent for patients with relapsed or refractory diffuse large B-cell lymphoma," said Jay Feingold, MD, PhD, Senior Vice President and Chief Medical Officer of ADC Therapeutics. "We’re also pleased that the updated data from the LOTIS-3 clinical trial demonstrate the encouraging antitumor activity and manageable toxicity profile of ZYNLONTA in combination with ibrutinib in patients with relapsed or refractory DLBCL or mantle cell lymphoma. We look forward to continued progress in all of our LOTIS trials, including the ongoing LOTIS-5 trial of ZYNLONTA in combination with rituximab and LOTIS-6 trial in patients with relapsed or refractory follicular lymphoma."

LOTIS-2 Follow-up Analysis (Poster 177)

In LOTIS-2, a single-arm, open-label, 145-patient Phase 2 clinical trial in patients with relapsed or refractory DLBCL who had failed ≥2 established therapies, ZYNLONTA demonstrated continued substantial antitumor activity and an acceptable safety profile. Updated results were presented in a poster by Pier Luigi Zinzani, MD, PhD, IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia "Seràgnoli", and Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Università di Bologna, Bologna, Italy. As of the data cut-off date of March 1, 2021, all patients had completed treatment.

Key data include:

Overall response rate (ORR) was 48.3% and complete response rate (CRR) was 24.8%
Median duration of response (mDoR) of 13.4 months for the 70 responders
Median duration of response not reached for patients with a complete response
Median overall survival was 9.5 months
No new safety concerns were identified during the study and no increase in toxicity was observed in patients aged ≥65 years compared with patients <65 years. The most common grade ≥3 treatment-emergent adverse events (TEAEs) were neutropenia (26.2%), thrombocytopenia (17.9%), increased gamma-glutamyltransferase (17.2%), and anemia (10.3%)
LOTIS-3 Updated Phase 1 Results (Poster 238)

LOTIS-3, a Phase 1/2, two-part, open-label, single-arm clinical trial, is evaluating ZYNLONTA in combination with ibrutinib in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or mantle cell lymphoma (MCL). Updated Phase 1 results were presented in a poster by Julien Depaus, MD, Department of Hematology, CHU UCL Namur site Godinne, Yvoir, Belgium. As of the data cut-off date of March 1, 2021, 30 patients with DLBCL (24 with non-germinal center B-cell (non-GCB) DLBCL and 6 with GCB DLBCL) and 7 patients with MCL were included in the study.

Key data include:

ORR in all patients was 62.2% and CRR was 35.1%
In non-GCB DLBCL patients, ORR was 66.7%
In GCB DLBCL patients, ORR was 16.7%
In MCL patients, ORR was 85.7%
ZYNLONTA in combination with ibrutinib had manageable toxicity, with the most common grade ≥3 TEAEs in ≥5% of patients being anemia (10.8%), neutropenia (10.8%), thrombocytopenia (5.4%), and fatigue (5.4%)
Pharmacokinetic profiles demonstrated sustained exposure and modest accumulation by Cycle 2
Two additional posters presented at the 16th Annual ICML

Phase 3 Randomized Study of Loncastuximab Tesirine plus Rituximab versus Immunochemotherapy in Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma – LOTIS-5 (Poster 251)
A Phase 2 Randomized Study of Loncastuximab Tesirine (Lonca) Versus (Vs) Idelalisib in Patients (Pts) with Relapsed or Refractory (R/R) Follicular Lymphoma (FL) – LOTIS-6 (Poster 264)
About ZYNLONTA (loncastuximab tesirine-lpyl)

ZYNLONTA is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death. The U.S. Food and Drug Administration (FDA) has approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. This indication is approved by the FDA under accelerated approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The FDA approval was based on data from LOTIS-2, a large (n=145) Phase 2 multinational, single-arm clinical trial of ZYNLONTA for the treatment of adult patients with r/r DLBCL following two or more prior lines of systemic therapy. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with very difficult to treat disease, including patients with high-grade B-cell lymphoma. The trial also enrolled patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, and patients who had stem cell transplants and CAR-T therapy prior to their treatment with ZYNLONTA. Results from the trial demonstrated an overall response rate (ORR) of 48.3% (70/145 patients), which included a complete response (CR) rate of 24.1% (35/145 patients) and a partial response (PR) rate of 24.1% (35/145 patients). Patients had a median time to response of 1.3 months. At the most recent data cut-off for patients enrolled in the trial, the median duration of response (mDoR) was 13.4 months. In a pooled safety population the most common adverse reactions (≥20%) were thrombocytopenia, gamma-glutamyltransferase increased, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea and musculoskeletal pain. In LOTIS-2, the most common (≥10%) grade ≥3 treatment-emergent adverse events were neutropenia (26.2%), thrombocytopenia (17.9%), gamma-glutamyltransferase increased (17.2%) and anemia (10.3%).

ZYNLONTA is being evaluated in combination for earlier lines of therapy and as a monotherapy in other B-cell malignancies.

On June 18, 2021 Ambrx, a clinical stage biopharmaceutical company using an expanded genetic code technology platform to discover and develop Engineered Precision Biologics (EPBs), reported the pricing of its initial public offering of 7,000,000 American depositary shares (ADSs), each representing seven ordinary shares, at a public offering price of $18.00 per ADS (Press release, Ambrx, JUN 18, 2021, View Source [SID1234584167]). The total gross proceeds to Ambrx from the offering are expected to be $126.0 million before deducting underwriting discounts and commissions and estimated offering expenses. In addition, Ambrx has granted the underwriters a 30-day option to purchase up to an additional 1,050,000 ADSs at the initial public offering price, less underwriting discounts and commissions. All of the ADSs are being offered by Ambrx. The shares are expected to begin trading on the New York Stock Exchange on June 18, 2021 under the ticker symbol "AMAM". The offering is expected to close on June 22, 2021, subject to the satisfaction of customary closing conditions.

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Goldman Sachs & Co. LLC, BofA Securities and Cowen are acting as joint book-running managers for the offering.

A registration statement relating to these securities was declared effective by the Securities and Exchange Commission on June 17, 2021. The offering is being made only by means of a written prospectus. A copy of the final prospectus relating to the offering, when available, may be obtained from: Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, or by telephone at (866) 471-2526, or by email at [email protected]; BofA Securities, Attention: Prospectus Department, NC1-004-03-43, 200 North College Street, 3rd Floor, Charlotte, NC 28255-0001, or by telephone at (800) 294-1322, or by email at [email protected]; or Cowen and Company, LLC, c/o Broadridge Financial Solutions, Attention: Prospectus Department, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (833) 297-2926, or by email at [email protected].

This press release shall not constitute an offer to sell, or the solicitation of an offer to buy, 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 June 18, 2021 Cyteir Therapeutics, Inc. ("Cyteir") (Nasdaq: CYT), a company focused on the discovery and development of next-generation synthetically lethal therapies for cancer, reported the pricing of its initial public offering of 7,400,000 shares of its common stock at an initial public offering price of $18.00 per share (Press release, Cyteir Therapeutics, JUN 18, 2021, View Source [SID1234584166]). All of the shares are being offered by Cyteir. In addition, Cyteir has granted the underwriters a 30-day option to purchase up to an additional 1,110,000 shares of common stock at the initial public offering price, less the underwriting discounts and commissions. The shares are scheduled to begin trading on The Nasdaq Global Select Market on June 18, 2021 under the ticker symbol "CYT."

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The gross proceeds of the offering, before deducting underwriting discounts and commissions and other estimated offering expenses payable by Cyteir, are expected to be approximately $133 million excluding any exercise of the underwriters’ option to purchase additional shares. The offering is expected to close on June 22, 2021, subject to the satisfaction of customary closing conditions.

J.P. Morgan, Morgan Stanley and BofA Securities are acting as joint book-running managers for the offering and Wedbush PacGrow is acting as co-manager.

A registration statement relating to the shares being sold in this offering was declared effective by the Securities and Exchange Commission on June 17, 2021. The offering is being made only by means of a prospectus. Copies of the final prospectus relating to the offering may be obtained, when available, for free by visiting EDGAR on the SEC website at www.sec.gov. Alternatively, copies of the final prospectus, when available, may be obtained from J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (866) 803-9204, or by email at [email protected]; Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, 2nd Floor, New York, NY 10014, or by telephone: 1-866-718-1649; or BofA Securities, Inc., NC1-004-03-43, 200 North College Street, 3rd Floor, Charlotte, NC 28255-0001, Attention: Prospectus Department or by email at: [email protected].

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

On June 18, 2021 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported its full year 2021 financial guidance to incorporate the GW Pharmaceuticals (GW) business, which the Company acquired on May 5, 2021 (Press release, Jazz Pharmaceuticals, JUN 18, 2021, View Source [SID1234584148]).

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"We expect 2021 to be another exciting, productive and transformational year for Jazz and are pleased to update our guidance to include the addition of GW. Our guidance reflects strong execution across our commercial portfolio, continued investment in both our ongoing and planned launches and strategic investments in R&D to advance therapies to patients in critical need of new treatment options. These investments will support the recent successful launches of both Xywav and Zepzelca, the ongoing growth of Epidiolex, the anticipated launches of JZP458 for ALL or LBL and Xywav in idiopathic hypersomnia, and the rolling launch of Epidyolex in Europe. As part of our continued R&D efforts we also look forward to advancing our PTSD and essential tremor programs, the nabiximols clinical trial program to support a U.S. regulatory approval, and our new cannabinoid research platform," said Renée Galá, chief financial officer of Jazz Pharmaceuticals. "We believe Epidiolex has near-term blockbuster potential and expect the addition of Epidiolex and the GW pipeline to deliver double-digit revenue growth, accelerated revenue diversification and substantial shareholder value. With the addition of GW, we are excited to transform the lives of even more patients and their families."

As a result of the acquisition, the Company expects:

Accelerated revenue diversification with double digit revenue growth; expect to generate 65% of 2022 revenues from products that have been launched or acquired since 20191
Earnings accretion, with the GW acquisition expected to be non-GAAP adjusted EPS accretive in the first full calendar year of combined operations and substantially accretive thereafter
Strong cash flows, which will enable rapid deleveraging, targeting less than 3.5x net leverage by the end of 2022
Continued investment in its broad and productive pipeline to drive long-term shareholder value
Additional value to be delivered through continued corporate development activity, while achieving deleveraging targets
2021 Financial Guidance2
The Company is updating its full year 2021 financial guidance for the combined organization, which includes the anticipated results of GW from May 5, 2021 to December 31, 2021.

Products acquired or launched since 2019 include Xywav, Epidiolex, Zepzelca and Sunosi, as well as the anticipated U.S. launches of JZP458 in acute lymphoblastic leukemia (ALL) / lymphoblastic lymphoma (LBL) and Xywav in idiopathic hypersomnia (in each case subject to FDA approval).
The Company’s 2021 financial guidance includes the anticipated results of the acquired GW business from the date of acquisition (May 5, 2021) and preliminary estimates of acquisition accounting adjustments related to the acquisition of GW, which estimates are subject to change; any such change could be material.
The Company expects the transaction to be dilutive to both GAAP and non-GAAP adjusted net income per diluted share in 2021. On a GAAP basis, this is expected to be primarily due to an increase in the amortization of acquisition-related intangible asset and transaction and integration expenses, the amortization of inventory fair value step-up, increased interest expense and the increase in number of outstanding shares relating to the GW acquisition. On a non-GAAP adjusted basis, this is expected to be due to increased cash interest expense and an increase in the number of outstanding shares.
Excludes $200-$225 million of amortization of acquisition-related inventory fair value step-up, $8-$10 million of share-based compensation expense and $2-$4 million of transaction and integration expenses relating to the GW acquisition from estimated GAAP gross margin.
Excludes $221-$245 million of transaction and integration expenses relating to the GW acquisition and $127-$135 million of share-based compensation expense from estimated GAAP SG&A expenses.
Excludes $35-$45 million of share-based compensation expense and $7-$11 million of transaction and integration expenses relating to the GW acquisition from estimated GAAP R&D expenses.
Excludes the income tax effect of adjustments between GAAP net income and non-GAAP adjusted net income.
See "Non-GAAP Financial Measures" below. Reconciliations of non-GAAP adjusted guidance measures are included above and in the table titled "Reconciliation of GAAP to Non-GAAP Adjusted 2021 Net Income Guidance" at the end of this press release.