As previously disclosed, on March 4, 2022, Mustang Bio, Inc. (the "Company") entered into a $75.0 million loan and security agreement (the "Loan Agreement") with Runway Growth Finance Corp., as a lender and as administrative agent and collateral agent for Lenders ("Runway") (Filing, 8-K, Mustang Bio, DEC 7, 2022, View Source [SID1234625216]).

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On December 7, 2022, the Company entered into the First Amendment (the "First Amendment") to the Loan Agreement by and between the Company and Runway. The First Amendment amended certain definitions and other provisions of the Loan Agreement to replace LIBOR-based benchmark rates applicable to loans outstanding under the Loan Agreement with SOFR-based rates, subject to adjustments as specified in the First Amendment.

The foregoing description of the First Amendment is not intended to be complete and is qualified in its entirety by reference to the full text of the First Amendment, a copy of which is filed as Exhibit 10.1, hereto and is incorporated by reference herein.

On December 7, 2022, Delcath Systems, Inc. ( the "Company") and certain accredited investors (each an "Investor" and collectively, the "Investors") entered into a securities purchase agreement (the "Securities Purchase Agreement") pursuant to which the Company agreed to sell and issue to the Investors in a private placement (the "Private Placement") (i) an aggregate of 1,448,889 shares (the "Shares") of the Company’s common stock, par value $0.01 per share (the "Common Stock"), at a purchase price of $2.90 per share, and (ii) in lieu of shares of Common Stock, 692,042 pre-funded warrants (the "Pre-Funded Warrants") to purchase Common Stock (the "Warrant Shares" and together with the Shares, the "Securities"), at a purchase price of $2.89 per Pre-Funded Warrant (Filing, Delcath Systems, DEC 7, 2022, View Source [SID1234625196]). The Pre-Funded Warrants will have an exercise price of $0.01 per share of Common Stock, be immediately exercisable and remain exercisable until exercised in full.

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The Private Placement closed on December 13, 2022. The Company received gross proceeds from the Private Placement of approximately $6.2 million, before deducting offering expenses payable by the Company. The Company intends to use the net proceeds of the Private Placement for working capital and other general corporate purposes.

The foregoing description of the Securities Purchase Agreement and the Pre-Funded Warrants does not purport to be complete and is qualified in its entirety by reference to the complete text of the Securities Purchase Agreement and the form of the Pre-Funded Warrant, which are attached hereto as Exhibits 10.1 and 4.1, respectively, to this Current Report on Form 8-K and are hereby incorporated by reference into this Item 1.01.

Registration Rights

In connection with the Private Placement, the Company and the Investors entered into a Registration Rights Agreement dated December 7, 2022 (the "Registration Rights Agreement"), providing for the registration for resale of the Securities (including the shares of Common Stock underlying the Pre-Funded Warrants) that are not then registered on an effective registration statement, pursuant to a registration statement (the "Registration Statement") to be filed with the Securities and Exchange Commission (the "SEC") on or prior to February 6, 2023 (the "Filing Date"). The Company has agreed to use its best efforts to cause the Registration Statement to be declared effective as soon as possible, but in no event later than 75 days of the closing of the Private Placement (or 120 days in the event of a full review of the Registration Statement by the SEC) (the "Effectiveness Date"), and to keep the Registration Statement continuously effective for a period that extends from the first date on which the SEC issues an order of effectiveness in relation to the Registration Statement until such date that all registrable securities (as such term is defined in the Registration Rights Agreement) covered by the Registration Statement have been sold thereunder or pursuant to Rule 144 or may be sold without volume or manner-of-sale restrictions pursuant to Rule 144 and without the requirement for the Company to be in compliance with the current public information requirement under Rule 144.

In the event (i) the Registration Statement is not filed on or prior to the Filing Date, or (ii) the Company fails to file with the SEC a request for acceleration of a registration statement in accordance with Rule 461 promulgated under the Act within five trading days of the date that the Company is notified by the SEC that the Registration Statement will not be "reviewed" or will not be subject to further review, or (iii) prior to the effective date of the Registration Statement, the Company fails to file a pre-effective amendment and otherwise respond in writing to comments made by the SEC in respect of such Registration Statement within fifteen calendar days after the receipt of comments by or notice from the SEC that such amendment is required in order for such Registration Statement to be declared effective, or (iv) the Registration Statement is not declared effective by the Effectiveness Date, or (v) after the effective date of the Registration Statement, it ceases for any reason to remain continuously effective as to the Securities, or the holders are otherwise not permitted to utilize the prospectus therein to resell the Securities, for more than fifteen consecutive calendar days or more than an aggregate of twenty calendar days during any 12-month period, then, until the applicable event is cured, the Company shall pay to each holder an amount in cash, as partial liquidated damages and not as penalty, equal to the product of 1.0% multiplied by the aggregate subscription amount paid by such holder pursuant to the Securities Purchase Agreement, subject to certain caps set forth in the Registration Rights Agreement.

The Company has granted the Investors customary indemnification rights in connection with the Registration Statement. The Investors have also granted the Company customary indemnification rights in connection with the Registration Statement.

The foregoing description of the Registration Rights Agreement does not purport to be complete and is qualified in its entirety by reference to the Registration Rights Agreement, a copy of which is filed as Exhibit 10.2 hereto and incorporated by reference into this Item 1.01.

Item 3.02
Unregistered Shares of Equity Securities.

The information contained above in Item 1.01 relating to the Private Placement is hereby incorporated by reference into this Item 3.02. Based in part upon the representations of the Investors in the Securities Purchase Agreement, the offering and sale of the securities was made in reliance on the exemption afforded by Regulation D under the Securities Act of 1933, as amended (the "Securities Act") and/or Regulation S under the Securities Act inasmuch as certain Investors are not a "U.S. person" (as defined in Rule 902 under the Securities Act) and the requirements of Rule 903 under the Securities Act are otherwise met, and corresponding provisions of state securities or "blue sky" laws. The Securities (including the shares of Common Stock underlying the Pre-Funded Warrants) have not been registered under the Securities Act or any state securities laws and may not be offered or sold in the United States absent registration with the SEC or an applicable exemption from the registration requirements. The sale of the Securities did not involve a public offering and was made without general solicitation or general advertising. The Investors represented that they are accredited investors, as such term is defined in Rule 501(a) of Regulation D under the Securities Act, and that they are acquiring the securities for investment purposes only and not with a view to any resale, distribution or other disposition of the securities in violation of the U.S. federal securities laws.

Neither this Current Report on Form 8-K nor any exhibit attached hereto is an offer to sell or the solicitation of an offer to buy shares of Common Stock or other securities of the Company.

On December 8, 2022 Nanology reported that it will be attending the following conference (Press release, NanOlogy, DEC 7, 2022, View Source;utm_medium=rss&utm_campaign=jan-9-13-jp-morgan-41st-annual-healthcare-conference-san-francisco [SID1234624956]):

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JP Morgan 41st Annual Healthcare Conference
Event: JP Morgan 41st Annual Healthcare Conference
Dates: January 9-11, 2023
Location: San Francisco

NanOlogy representatives will be in San Francisco January 9-11 for JPM/Biotech Showcase Week. Email [email protected] if you would like to schedule a meeting or contact us through the Biotech Showcase Partnering Platform. NanOlogy is a clinical-stage oncology company with a proprietary particle engineering technology that forms patented large surface area microparticles (LSAMS) of pure drug for solid tumor-directed delivery to maximize drug in the tumor and minimize systemic toxicity. Clinical trials in multiple solid tumors (pancreas, lung, bladder, prostate, ovarian, peritoneal) across more than 170 patients to date have demonstrated promising tumor response and immunomodulation with minimal toxicity.

On December 7, 2022 KSQ Therapeutics, a clinical-stage biotechnology company developing therapies to treat cancer and autoimmune diseases using its proprietary, integrated discovery CRISPRomics platform, reported the initiation of dosing in the combination therapy portion of Study KSQ-4279-1101, a Phase 1 clinical study of KSQ-4279 in patients with advanced solid tumors (Press release, KSQ Therapeutics, DEC 7, 2022, View Source [SID1234624922]). This stage of the clinical study will investigate KSQ-4279 across multiple indications, both in combination with a PARP inhibitor and in combination with chemotherapy.

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"The initiation of the combination therapy portion of the study is a significant milestone for KSQ. We are excited by the strong combination activity that we observed across multiple preclinical models in both BRCA-mutant ovarian and triple-negative breast cancers, including models from patients that relapsed after multiple rounds of chemotherapy and treatment with PARP inhibitors," said Andrew Wylie, Ph.D., Senior Vice President, Head of Oncology at KSQ. "We continue to see strong evidence of the promise and potential of our CRISPRomics platform, and believe we are just beginning to realize the tremendous opportunities to develop therapies with true curative potential for a wide range of cancers, in particular solid tumors, as well as autoimmune diseases."

"The preclinical data suggests there is a broad opportunity to combine KSQ-4279 with PARP inhibitors and with chemotherapy," said Qasim Rizvi, Chief Executive Officer of KSQ. "The safety profile was favorable in preclinical studies, and KSQ-4279 has been well-tolerated in the ongoing Phase 1 clinical trial. No dose-limiting toxicities have been reported to date in the monotherapy dose escalation portion of the clinical trial. In addition, KSQ-4279 has demonstrated tumor growth inhibition as a single agent and led to deep and durable tumor regressions when administered in combination with a PARP inhibitor in multiple preclinical tumor models."

KSQ-4279 preclinical data highlights:

KSQ-4279 is active as a monotherapy in BRCA1-mutant ovarian PDX models, with tumor regressions observed at doses well below its maximum tolerated dose.
KSQ-4279 activity is seen in cancers that harbor defects in homologous recombination (HR), a genetic driver event prevalent in several solid tumor types.
In patient-derived TNBC xenograft models resistant to PARP inhibitor treatment, combining KSQ-4279 with a PARP inhibitor led to durable tumor regressions.
Data presented at the recent ENA 2022 conference described the activity of KSQ-4279 in ovarian tumor ascites models derived from patient tumors that had relapsed after multiple rounds of chemotherapy, including, in some cases, PARP inhibitor therapy.
Four of the ovarian models tested had BRCA1 mutations but were resistant to PARP inhibitor therapy, yet all four were sensitive to KSQ-4279 when used in combination with a PARP inhibitor.
KSQ utilized its proprietary CRISPRomics platform to identify the deubiquitinating enzyme USP1 as an attractive cancer target with established roles in DNA damage repair processes that are distinct from PARP inhibitors and other approaches currently being tested in the clinic. Potent and highly selective inhibitors of USP1 were developed, and profiling of the clinical development candidate KSQ-4279 across a large collection of tumor models confirmed an enriched response rate in cancers with genetic alterations in BRCA1/2 or other HRD lesions.

Study KSQ-4279-1101 is a Phase 1 clinical trial expected to enroll approximately 140 patients with advanced solid tumors. It is a dose-escalation and expansion trial of KSQ-4279 as a monotherapy and in combination. The study’s primary endpoint is to assess the safety of KSQ-4279 both alone and in combination, determine the maximum tolerated dose, and establish a recommended Phase 2 dose. Secondary endpoints include characterizing the pharmacokinetics of KSQ-4279 and evaluating its preliminary antitumor activity alone and in combination. The trial will also explore potential predictive biomarkers and other genetic factors and their correlation with clinical outcomes.

KSQ-4279

KSQ-4279 is a first-in-class small molecule targeting USP1, a protein regulating DNA damage response (DDR). USP1 was identified by KSQ’s CRISPRomics platform as a novel synthetic lethal target in cancers with certain types of genomic instability. KSQ-4279 is currently being evaluated in a Phase 1 study in patients with advanced solid tumors.

On December 7, 2022 Updated results from the DESTINY-Breast03 phase 3 trial (Abstract #GS2-02) reported that ENHERTU (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared to trastuzumab emtansine (T-DM1) in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane (Press release, AstraZeneca, DEC 7, 2022, View Source [SID1234624921]). These results and primary results from the DESTINY-Breast02 phase 3 trial (Abstract #GS2-01) will be presented today at the 2022 San Antonio Breast Cancer Symposium (#SABCS22), with the updated results from DESTINY-Breast03 simultaneously published in The Lancet.

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ENHERTU is a specifically engineered HER2 directed antibody drug conjugate (ADC) being jointly developed and commercialized by Daiichi Sankyo (TSE:4568) and AstraZeneca (LSE/STO/Nasdaq: AZN).

In the key secondary endpoint analysis of OS in DESTINY-Breast03, ENHERTU demonstrated a 36% reduction in risk of death versus T-DM1 (hazard ratio [HR] = 0.64; 95% confidence interval [CI] 0.47-0.87; p=0.0037). In both treatment arms, median OS was not yet reached (ENHERTU [40.5-NE] versus T-DM1 [34.0-NE]) after a median duration of follow-up of 28.4 months for ENHERTU and 26.5 months for T-DM1. In the ENHERTU arm, an estimated 77.4% of patients were alive at two years (95% CI: 71.7-81.2) compared to 69.9% of patients treated with T-DM1 (95% CI: 63.7-75.2). The observed survival benefit was consistent across all analyzed subgroups, including patients with or without baseline brain metastases, with or without baseline visceral disease, those who were hormone receptor (HR) positive or HR negative and patients regardless of prior pertuzumab or lines of systemic therapy.

"The main goals of therapy for advanced breast cancer are to control the disease and improve survival, and it is therefore critical to continue to improve upon existing treatment options, particularly in the metastatic setting," said Sara Hurvitz, MD, Medical Oncologist, Professor of Medicine and Director of the Breast Cancer Clinical Trials Program in the Division of Hematology-Oncology at the David Geffen School of Medicine at UCLA, and Medical Director for the Clinical Research Unit at the UCLA Jonsson Comprehensive Cancer Center in Santa Monica, CA. "For patients with HER2 positive breast cancer who experience disease progression following initial treatment in the metastatic setting, ENHERTU has shown significant improvement in survival compared to T-DM1, further confirming this medicine as the new standard of care."

With the additional follow-up in DESTINY-Breast03, ENHERTU also continued to demonstrate a clinically meaningful improvement in progression-free survival (PFS) with a 22 month improvement in median PFS over T-DM1, reaffirming the statistically significant finding at the previous interim analysis. The updated exploratory analysis was not tested for statistical significance and not powered to show differences between treatment arms. The median PFS for patients in the ENHERTU arm was 28.8 months (HR=0.33; 95% CI: 22.4-37.9) compared to 6.8 months for T-DM1 (95% CI: 5.6-8.2) as assessed by blinded independent central review (BICR). Confirmed objective response rate (ORR) was 78.5% in the ENHERTU arm with 21.1% of patients demonstrating a complete response (CR) versus an ORR of 35.0% in the T-DM1 arm where 9.5% of patients achieved a CR. The median duration of response (DoR) was 36.6 months in the ENHERTU arm and 23.8 months in the T-DM1 arm.

The safety profile observed with ENHERTU in DESTINY-Breast03 was consistent with previous clinical trials with no new safety concerns identified. Grade 3 or higher treatment-related treatment emergent adverse events (TEAEs) occurred in 47.1% of patients receiving ENHERTU. The most common grade 3 or higher treatment-related TEAEs in the ENHERTU arm were decreased neutrophil count (16.0%), anemia (9.3%), decreased platelet count (7.8%), nausea (7.0%), decreased white blood cell count (6.2%) and fatigue (5.8%). In the ENHERTU arm, 15.2% of patients (n=39) experienced interstitial lung disease (ILD) or pneumonitis related to treatment as determined by an independent adjudication committee. The majority of ILD or pneumonitis events were low grade (grade 1 or grade 2) with two grade 3 events and no grade 4 or grade 5 events observed in patients treated with ENHERTU.

"The overall survival benefits shown in both the DESTINY-Breast03 and DESTINY-Breast02 trials further validate the role of ENHERTU in potentially extending the lives of patients with previously treated HER2 positive breast cancer," said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. "Additionally, median progression-free survival was four times longer with one in five patients showing no detectable signs of disease when treated with ENHERTU compared to T-DM1 in DESTINY-Breast03, which is particularly impressive in the metastatic setting of HER2 positive breast cancer."

"The updated results for DESTINY-Breast03 showing that ENHERTU extends patients’ lives and also delays progression by nearly two years reinforces our belief that this medicine has the potential to set a new standard of care for patients with HER2 positive metastatic breast cancer treated in the second-line setting," said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology R&D, AstraZeneca. "Complemented by DESTINY-Breast02, we now have two phase 3 trials in HER2 positive metastatic breast cancer showing patients in these trials have more disease-free time and live longer when they receive ENHERTU versus the previous standard of care."

All patients in DESTINY-Breast03 received at least one prior cancer therapy, including trastuzumab (ENHERTU = 99.6%; T-DM1 = 99.6%) or pertuzumab (ENHERTU = 62.1%; T-DM1 = 60.1%). In the ENHERTU arm, 41.4% of patients had received one prior line of therapy in the metastatic setting. At baseline, 16.5% of patients in the ENHERTU arm and 14.8% of patients in the T-DM1 arm had a history of brain metastases. As of data cut-off on July 25, 2022, 75 patients remained on treatment with ENHERTU and 18 patients on T-DM1.

Summary of Updated DESTINY-Breast03 Results

Efficacy Measure

ENHERTU (5.4 mg/kg)

n=261

Trastuzumab Emtansine
(T-DM1; 3.6 mg/kg)

n=263

Median OS, months (95% CI)

Not reached (40.5-NE)

Not reached (34.0-NE)

HR=0.64 (0.47-0.87) p=0.0037i

OS rate (%) (95% CI)

12 months

94.1% (90.4-96.4)

86.0% (81.1-89.8)

24 months

77.4 % (71.7-82.1)

69.9% (63.7-75.2)

Median PFS by BICR, months (95% CI)

28.8 months (22.4-37.9)

6.8 months (5.6-8.2)

HR=0.33 (0.26-0.43) p<000001i,ii

Median PFS2 by investigator, months (95% CI)iii

40.5 months (40.5-NE)

25.7 months (18.5-34.0)

HR=0.47 (0.35-0.62) p=0.000001i,ii

Confirmed ORR, % (95% CI)

78.5% (73.1-83.4)

35.0% (29.2-41.1)

p<0.0001i,ii

CR (%)

21.1% (n=55)

9.5% (n=25)

PR (%)

57.5% (n=150)

25.5% (n=67)

SD (%)

18.0% (n=47)

41.8% (n=110)

PD (%)

1.1% (n=3)

17.9% (n=47)

Median DoR, months (95% CI)iv

36.6 months (22.4-NE)

23.8 months (12.6-34.7)

BICR, blinded independent central review; CI, confidence interval; CR, complete response, DoR, duration of response; ORR, objective response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PFS2, second progression-free survival; PR, partial response; SD, stable disease

i Two-sided

ii Nominal p value. Updated exploratory analysis was not tested for statistical significance and not powered to show differences between treatment arms

iii From the time of randomization to second progression

iv Based on BICR

DESTINY-Breast02 Primary Results
In the primary results from the DESTINY-Breast02 phase 3 trial, ENHERTU demonstrated a 64% reduction in the risk of disease progression or death in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with T-DM1 compared to physician’s choice of treatment (trastuzumab plus capecitabine or lapatinib plus capecitabine) (HR=0.36; 95% CI: 0.28-0.45; p<0.000001). The median PFS for patients in the ENHERTU arm was 17.8 months (95% CI: 14.3-20.8) compared to 6.9 months (95% CI: 5.5-8.4) for those treated with physician’s choice of therapy as assessed by BICR. Treatment with ENHERTU also showed a 34% reduction in the risk of death compared to physician’s choice of treatment (HR=0.66; 95% CI: 0.50-0.86; p=0.0021) with a median OS of 39.2 months with ENHERTU (95% CI: 32.7-NE) versus 26.5 months with physician’s choice of therapy (95% CI: 21.0-NE).

The data from DESTINY-Breast02 confirm the data seen in the DESTINY-Breast01 phase 2 trial, which supported the first approvals of ENHERTU in patients with HER2 positive metastatic breast cancer who received two or more prior anti-HER2-based regimens.

The safety profile observed with ENHERTU in DESTINY-Breast02 was consistent with previous clinical trials with no new safety concerns identified. Grade 3 or higher treatment-related TEAEs occurred in 41.3% of patients receiving ENHERTU. The most common grade 3 or higher treatment-related TEAEs in the ENHERTU arm were decreased neutrophil count (10.6%), anemia (7.9%), neutropenia (7.7%), nausea (6.7%) and asthenia (5.0%). In the ENHERTU arm, 10.4% of patients (n=42) experienced ILD or pneumonitis related to treatment as determined by an independent adjudication committee. The majority of ILD or pneumonitis events were low grade (grade 1 or grade 2), with three grade 3 events, no grade 4 events and two grade 5 events observed.

About DESTINY-Breast03
DESTINY-Breast03 is a global, head-to-head, randomized, open-label, pivotal phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) versus T-DM1 in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. The primary efficacy endpoint of DESTINY-Breast03 is PFS based on BICR. OS is a key secondary efficacy outcome measure. Other secondary endpoints include ORR, DoR, PFS based on investigator assessment and safety. DESTINY-Breast03 enrolled 524 patients at multiple sites in Asia, Europe, North America, Oceania and South America. Primary results from DESTINY-Breast03 were published in The New England Journal of Medicine, with updated OS results published in The Lancet. For more information about the trial, visit ClinicalTrials.gov.

About DESTINY-Breast02
DESTINY-Breast02 is a global, randomized, open-label, pivotal phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) versus physician’s choice of treatment (trastuzumab/capecitabine or lapatinib/capecitabine) in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with T-DM1. Patients were randomized 2:1 to receive either ENHERTU or physician’s choice of treatment. The primary endpoint of DESTINY-Breast02 is PFS based on BICR. The key secondary endpoint is OS. Other secondary endpoints include ORR based on BICR and investigator assessment, DoR based on BICR, PFS based on investigator assessment and safety. DESTINY-Breast02 enrolled approximately 600 patients at multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

About HER2 Positive Breast Cancer
Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed in 2020, with nearly 685,000 deaths globally.1 Approximately one in five cases of breast cancer are considered HER2 positive.2

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancers.3 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.4

Despite initial treatment with trastuzumab and a taxane, patients with HER2 positive metastatic breast cancer will often experience disease progression.5,6

About ENHERTU
ENHERTU (trastuzumab deruxtecan, fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

ENHERTU (5.4 mg/kg) is approved in more than 35 countries for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received a (or one or more) prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial. ENHERTU also is approved in several countries for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.

ENHERTU (5.4 mg/kg) is approved in Brazil and the U.S. for the treatment of adult patients with unresectable or metastatic HER2 low (immunohistochemistry (IHC) 1+ or IHC 2+/in-situ hybridization (ISH)-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

ENHERTU (5.4 mg/kg) is approved under accelerated approval in the U.S. for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a FDA-approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ENHERTU (6.4 mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

ENHERTU is approved in the U.S. with Boxed WARNINGS for Interstitial Lung Disease and Embryo-Fetal Toxicity. For more information, please see the accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

About the ENHERTU Clinical Development Program
A comprehensive global development program is underway evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2 targetable cancers including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, also are underway.

Regulatory applications for ENHERTU in breast and gastric cancer are currently under review in several countries.