On December 12, 2019 Aurinia Pharmaceuticals Inc. (NASDAQ:AUPH) (TSX:AUP) ("Aurinia" or the "Company"), a late-stage clinical biopharmaceutical company focused on advancing voclosporin in multiple indications, reported the closing of its previously announced underwritten public offering of 12,782,439 common shares, including 1,667,274 common shares pursuant to the full exercise of the underwriters’ option to purchase additional common shares (the "Offering") (Press release, Aurinia Pharmaceuticals, DEC 12, 2019, View Source [SID1234552310]). The shares were sold at a public offering price of US$15.00 per share. The gross offering proceeds to the Company from this Offering are approximately US$191.7 million, before deducting underwriting discounts and commissions and other estimated offering expenses.

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Jefferies LLC and SVB Leerink LLC acted as joint book-running managers for the Offering. H.C. Wainwright & Co. LLC, Oppenheimer & Co. Inc., and Bloom Burton Securities Inc. acted as co-managers for the Offering.

For the purposes of the TSX approval, the Company relied on the exemption set forth in Section 602.1 of the TSX Company Manual, which provides that the TSX will not apply its standards to certain transactions involving eligible inter-listed issuers on a recognized exchange, such as NASDAQ.

The Company intends to use the net proceeds of the Offering for pre-commercialization and launch activities, as well as working capital and general corporate purposes.

The Offering was made pursuant to a U.S. registration statement on Form F-10, declared effective by the United States Securities and Exchange Commission (the "SEC") on March 29, 2018 (the "Registration Statement"), and the Company’s existing Canadian short form base shelf prospectus (the "Base Shelf Prospectus") dated March 26, 2018. The prospectus supplements relating to the Offering (together with the Base Shelf Prospectus and the Registration Statement, the "Offering Documents") have been filed with the securities commissions in the provinces of British Columbia, Alberta and Ontario in Canada, and with the SEC in the United States. The Offering Documents contain important detailed information about the securities being offered. Before you invest, you should read the Offering Documents and the other documents the Company has filed for more complete information about the Company and the Offering. Copies of the Offering Documents are available for free by visiting the Company’s profiles on the SEDAR website maintained by the Canadian Securities Administrators at www.sedar.com or the SEC’s website at www.sec.gov, as applicable. Alternatively, copies of the prospectus supplement are available upon request by contacting Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022; by phone at (877) 821-7388; or by e-mail at [email protected]; or SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at 1-800-808-7525, ext. 6132, or by email at [email protected].

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

On December 12, 2019 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported the presentation of interim data from the ongoing, investigator-sponsored Phase 1b clinical study of cirmtuzumab, its investigational anti-ROR1 monoclonal antibody, in combination with paclitaxel in patients with HER2-negative, metastatic or locally-advanced unresectable breast cancer (Press release, Oncternal Therapeutics, DEC 12, 2019, View Source [SID1234552329]). The results were presented at the San Antonio Breast Cancer Symposium (SABCS) in San Antonio, TX. A copy of the poster presentation is available online at www.oncternal.com.

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As of the data cut-off date of November 27, 2019, a total of eight patients with HER2-negative, metastatic or locally-advanced unresectable breast cancer were enrolled in the study. Seven of the eight patients were evaluable for safety and efficacy. Four of the patients had triple negative breast cancer (TNBC) at study enrollment.

Four of the seven evaluable patients achieved a partial response, for an objective response rate of 57%, including one partial response that continued on cirmtuzumab alone for 30 weeks after discontinuing paclitaxel.

The combination of cirmtuzumab and paclitaxel has been well tolerated in this trial, with no study discontinuations for toxicity and no dose-limiting toxicities observed to date. Adverse events have been consistent with the known safety profile of paclitaxel alone.

Pharmacokinetic analysis of serial plasma samples for free unbound antibody from two patients provided results similar to those observed in previous studies of chronic lymphocytic leukemia patients, consistent with a projected half-life of 30 days. No decline in antibody concentration over time was observed, consistent with the absence of neutralizing antibodies.

"It is encouraging to see that cirmtuzumab in combination with paclitaxel has been well tolerated and is active. Future studies will determine whether cirmtuzumab is contributing to the known activity of paclitaxel. Advanced breast cancer patients are in need of improved treatment options with acceptable side effects. We look forward to completing enrollment and treating additional patients in this study," said Rebecca Shatsky, M.D., Assistant Clinical Professor, Medicine at University of California San Diego School of Medicine, lead investigator who presented the poster.

Funding for this trial was provided by Oncternal Therapeutics, California Institute for Regenerative Medicine, UC San Diego Alpha Stem Cell Clinic and Sanford Stem Cell Clinical Center, UC San Diego Moores Cancer Center, Padres Pedal the Cause Grant, and Gonick Breast Cancer Research Funds.

"The early activity signals for cirmtuzumab in combination with paclitaxel for patients with breast cancer seen in this study are encouraging. We believe these data, taken together with the previously updated clinical data in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) from the CIRLL study presented at the annual ASH (Free ASH Whitepaper) meeting, reinforce the encouraging safety data and provide evidence of clinical activity of cirmtuzumab and its potential for the treatment of patients with breast cancer and other ROR1-expressing solid tumors and hematological malignancies," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO.

About the Clinical Trial

This clinical trial is an investigator-sponsored Phase 1b Pilot Clinical Trial of Cirmtuzumab, an Anti-ROR1 Monoclonal Antibody, in Combination with Paclitaxel for the Treatment of Patients with Metastatic, or Locally Advanced, Unresectable Breast Cancer. The objectives of the trial include the evaluation of safety, tolerability, pharmacokinetics, and clinical activity. Eligible patients are those with locally-advanced, unresectable or metastatic HER2-negative breast cancer who had not received paclitaxel in the metastatic setting. Study treatment included a fixed dose of 600 mg cirmtuzumab given on days 1 and 15 of cycle 1, and then on day 1 of each subsequent 28-day cycle. Paclitaxel was given weekly at a dose of 80 mg/m2. Additional information about the clinical trial may be accessed at ClinicalTrials.gov (NCT02776917).

About Cirmtuzumab

Cirmtuzumab is an investigational, potentially first-in-class monoclonal antibody targeting ROR1, or Receptor tyrosine kinase-like Orphan Receptor 1. Cirmtuzumab is currently being evaluated in a Phase 1/2 clinical trial in combination with ibrutinib for the treatment of CLL or MCL, in a collaboration with the UC San Diego School of Medicine and the California Institute for Regenerative Medicine (CIRM). In addition, an investigator-initiated Phase 1 clinical trial of cirmtuzumab in combination with paclitaxel for women with metastatic breast cancer is being conducted at the UC San Diego School of Medicine. CIRM has also provided funding to support development programs for cirmtuzumab and a CAR-T therapy that targets ROR1, which is currently in preclinical development as a potential treatment for hematologic cancers and solid tumors.

ROR1 is a potentially attractive target for cancer therapy because it is an oncofetal antigen – a protein that confers a survival and fitness advantage when reactivated and expressed by tumor cells. When expressed by hematologic malignancies such as CLL and MCL, ROR1 acts as a receptor for the tumor growth factor Wnt5a. Researchers at the UC San Diego School of Medicine discovered that targeting a critical epitope on ROR1 was key to inhibiting Wnt5a activation, specifically targeting ROR1 expressing tumors. This led to the development of cirmtuzumab that binds this critical epitope of ROR1, which is highly expressed on many different cancers but not on normal tissues. Preclinical data showed that when cirmtuzumab bound to ROR1, it blocked Wnt5a signaling, inhibited tumor cell proliferation, migration and survival, and induced differentiation of the tumor cells. Cirmtuzumab is in clinical development and has not been approved by the U.S. Food and Drug Administration for any indication.

On December 12, 2019 Centene Corporation (NYSE: CNC) reported its 2020 financial guidance (Press release, Centene , DEC 12, 2019, View Source [SID1234552330]). Total revenues are expected to be $78.6 billion to $79.4 billion, and diluted earnings per share are expected to be $4.17 to $4.33. Adjusted diluted earnings per share for 2020 are expected to be $4.64 to $4.84.

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For its 2020 fiscal year, the Company’s guidance is as follows:

Total revenues in the range of approximately $78.6 billion to $79.4 billion.
Diluted earnings per share of approximately $4.17 to $4.33.
Adjusted diluted earnings per share of approximately $4.64 to $4.84.
Health benefits ratio of approximately 86.0% to 86.5%.
Selling, general and administrative (SG&A) expense ratio of approximately 9.2% to 9.7%.
Adjusted SG&A expense ratio of approximately 9.1% to 9.6%, which excludes $15 million to $25 million of acquisition related expenses.
Effective tax rate of approximately 34.0% to 36.0%.
Diluted shares outstanding of approximately 422.5 million to 424.5 million.
"We are on track to close another successful year at Centene, as a result of strong execution across our product and market portfolio," said Michael Neidorff, Chairman, President and CEO of Centene. "We look ahead at 2020 well-positioned to continue to deliver on our growth strategy with strong top and bottom-line performance. It will be a transformational year for Centene as we look forward to completing the WellCare transaction and solidify our place as the premier government-sponsored healthcare enterprise. We remain focused on enhancing our ability to serve our members and improving their health, while creating significant value for our shareholders."

The Company’s 2020 guidance excludes the pending WellCare acquisition, associated one-time integration costs, the related financing and closing costs, and the impact of the previously announced divestitures. The acquisition is subject to regulatory approval and is expected to close in the first half of 2020. The Company’s 2020 guidance includes acquisition related expenses of $15 million to $25 million for legal and integration planning expenses. Additionally, our 2020 guidance reflects a delay in the North Carolina start date from February 1, 2020 to October 1, 2020, resulting in a reduction of revenues of approximately $500 million and diluted earnings per share of approximately $0.06.

The Company affirms its 2019 total revenues guidance in the previously announced range of $73.6 billion to $74.2 billion, updates its 2019 diluted earnings per share guidance to a range of approximately $3.01 to $3.18, and affirms its 2019 adjusted diluted earnings per share guidance of approximately $4.29 to $4.49. The 2019 diluted earnings per share guidance was decreased by $0.03 to reflect the net carrying cost of the $7.0 billion issuance of senior notes completed in December in preparation for the WellCare acquisition. The net carrying costs include the related interest expense and corresponding investment income. Full year 2019 earnings will be reported on February 4, 2020, at 6:00 AM, with a conference call at 8:30 AM (Eastern Time).

Investor Meeting

Centene Corporation will host an investor meeting tomorrow at the Pierre Hotel in New York City, including a question-and-answer session, to discuss the details of its guidance. The event will begin promptly at 8:30 AM (Eastern Time) and end at approximately 12:30 PM (Eastern Time). Investors and other interested parties who are unable to attend in person are invited to listen to the investor meeting via a live, audio webcast on the Company’s website and view a copy of the investor presentation at www.centene.com, under the Investors section.

Non-GAAP Financial Presentation

The Company is providing certain non-GAAP financial measures in this release as the Company believes that these figures are helpful in allowing investors to more accurately assess the ongoing nature of the Company’s operations and measure the Company’s performance more consistently across periods. The Company uses the presented non-GAAP financial measures internally to allow management to focus on period-to-period changes in the Company’s core business operations. Therefore, the Company believes that this information is meaningful in addition to the information contained in the GAAP presentation of financial information. The presentation of this additional non-GAAP financial information is not intended to be considered in isolation or as a substitute for the financial information prepared and presented in accordance with GAAP. The Company references Adjusted SG&A Expense Ratio guidance, however the Company cannot provide a reconciliation of Adjusted SG&A Expense Ratio guidance without unreasonable efforts. As such, it has been excluded from the reconciliation below.

Specifically, the Company believes the presentation of non-GAAP financial information that excludes amortization of acquired intangible assets, acquisition related expenses, as well as other items, allows investors to develop a more meaningful understanding of the Company’s performance over time. The table below provides reconciliations of non-GAAP items per share:

Annual Guidance December 31, 2019

The amortization of acquired intangible assets per diluted share presented above are net of the income tax benefit of an estimated $0.14 for the year ended December 31, 2019 and $0.13 to $0.14 for the year ended December 31, 2020.

The acquisition related expenses per diluted share presented above are net of the income tax benefit of an estimated $0.07 for the year ended December 31, 2019 and an estimated $0.01 to $0.02 for the year ended December 31, 2020. Acquisition related expenses for 2019 include net carrying costs on the $7.0 billion senior notes issued in preparation of the WellCare acquisition of approximately $15 million, or $0.03 per diluted share, net of an income tax benefit of approximately $0.01.

Other adjustments for 2019 include the following: non-cash goodwill and intangible asset impairment of $271 million or $0.57 per diluted share, net of an income tax benefit of $0.08 and debt extinguishment costs of $29 million or $0.05 per diluted share, net of an income tax benefit of approximately $0.02.

On December 12, 2019 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported new data from the Phase III FeDeriCa study which showed the investigational fixed-dose combination (FDC) of Perjeta (pertuzumab) and Herceptin (trastuzumab) with hyaluronidase, administered by subcutaneous (SC) injection in combination with intravenous (IV) chemotherapy, demonstrated non-inferior levels of Perjeta in the blood (pharmacokinetics) and comparable efficacy and safety to standard IV infusions of Perjeta plus Herceptin and chemotherapy in eligible people with HER2-positive early breast cancer (EBC) (Press release, Genentech, DEC 12, 2019, View Source [SID1234552277]).

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These new data, from a primary analysis of the FeDeriCa study, will be presented in a spotlight session (Abstract #PD4-07) at 7:00 a.m. CST today at the 2019 San Antonio Breast Cancer Symposium (SABCS).

SC administration of the FDC takes approximately eight minutes for the initial loading dose and approximately five minutes for each subsequent maintenance dose. This is compared to approximately 150 minutes for infusion of a loading dose of Perjeta and Herceptin using the standard IV formulations, and between 60-150 minutes for subsequent maintenance infusions of the two medicines.

"This fixed-dose subcutaneous combination has the potential to provide a quicker and less invasive method of administration for people with HER2-positive breast cancer being treated with Perjeta and Herceptin," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "This is the first time that we have brought together two of our targeted antibodies as a single subcutaneous injection that can be administered in just minutes."

The FeDeriCa study met its primary endpoint, with SC administration of the FDC showing non-inferior levels of Perjeta in the blood during a given dosing interval (Ctrough) when compared to IV administration of Perjeta. The geometric mean ratio (GMR, a type of average used when assessing pharmacokinetics) for the primary endpoint was 1.22 (90% CI 1.14-1.31) with the lower limit of the 90% CI of the GMR=1.14≥0.80 (the pre-specified non-inferiority margin). A secondary endpoint of non-inferior Ctrough of Herceptin was also met, with blood concentrations for people receiving the FDC non-inferior to those receiving IV Herceptin (GMR=1.33 [90% CI 1.24-1.43]; lower limit of 90% CI of GMR=1.24≥0.80). A non-inferiority endpoint was chosen for the study to ensure that people were receiving sufficient dosing with Perjeta and Herceptin as compared to the established IV doses at the same treatment intervals. In addition, rates of total pathological complete response (pCR), a secondary endpoint, were comparable between the treatment arms, with 59.7% of patients receiving the FDC and 59.5% of patients treated with IV Perjeta and Herceptin achieving a total pCR – a difference of 0.15% (95% CI -8.67-8.97).

The safety profile of the FDC in combination with chemotherapy was comparable to that of IV administration of Perjeta plus Herceptin and chemotherapy, and no new safety signals were identified, including no meaningful difference in cardiac toxicity. The most common adverse events in both arms were alopecia, nausea, diarrhea and anemia.

In previous studies, SC administration has been shown to be strongly preferred by the majority of patients compared to IV administration of the same medicine, with the most common reason being that administration required less time in the clinic. In the PHranceSCa study, Genentech is currently investigating patient preference for SC administration of the FDC compared to standard IV administration of Perjeta and Herceptin in people with HER2-positive EBC. Interim results of this Phase II study will be presented at a future medical meeting.

About the FeDeriCa study

FeDeriCa is an international, multicenter, two-arm, randomized, open-label, Phase III study evaluating the pharmacokinetics, efficacy and safety of SC injection of the FDC of Perjeta and Herceptin in combination with chemotherapy, compared with standard IV infusions of Perjeta and Herceptin in combination with chemotherapy in 500 people with HER2-positive EBC who are being treated in the neoadjuvant (before surgery) and adjuvant (after surgery) settings. The primary endpoint of the study is minimum levels of Perjeta in the blood during a given dosing interval (Ctrough). Secondary endpoints include safety; minimum levels of Herceptin in the blood during a given dosing interval (Ctrough); and total pCR, meaning there is no tumor tissue detectable in the tissue removed at the time of surgery. The safety profile of Perjeta and Herceptin FDC was comparable with that of Perjeta and Herceptin administered intravenously.

About HER2-positive breast cancer

Breast cancer is one of the most common cancers among women worldwide. According to the American Cancer Society, approximately 271,000 people in the United States will be diagnosed with breast cancer, and more than 42,000 will die from the disease in 2019. Breast cancer is not one, but many diseases based on the biology of each tumor. In HER2-positive breast cancer, there is excess HER2 protein on the surface of tumor cells. Approximately 15-20% of breast cancers are HER2-positive based on the result of a diagnostic test.

About the FDC of Perjeta and Herceptin

The FDC of Perjeta and Herceptin is a new SC formulation that combines Perjeta and Herceptin with Halozyme Therapeutics’ Enhanze drug delivery technology.

Trastuzumab in the FDC is the same monoclonal antibody as in IV Herceptin and pertuzumab in the FDC is the same monoclonal antibody as in IV Perjeta. The mechanisms of action of Perjeta and Herceptin are believed to complement each other as both bind to the HER2 receptor, but in different locations. The combination of Perjeta and Herceptin is thought to provide a more comprehensive, dual blockade of the HER signaling pathways.

Halozyme’s Enhanze drug delivery technology may enable and optimize SC drug delivery for appropriate co-administered therapeutics. The technology is based on a proprietary recombinant human hyaluronidase PH20 (rHuPH20), an enzyme that temporarily degrades hyaluronan – a glycosaminoglycan or chain of natural sugars in the body, to aid in the dispersion and absorption of other injected therapeutic drugs.

Current Perjeta and Herceptin IV Indication Statements and Important Safety Information

Perjeta Indication Statements

Perjeta (pertuzumab) is a prescription medicine approved for use in combination with Herceptin (trastuzumab) and chemotherapy for:

use prior to surgery (neoadjuvant treatment) in people with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (tumor is greater than two centimeters in diameter or node-positive). Perjeta should be used as part of a complete treatment regimen for early breast cancer.
use after surgery (adjuvant treatment) in people with HER2-positive early breast cancer that has a high likelihood of coming back.
Perjeta (pertuzumab) is a prescription medicine approved for use in combination with Herceptin (trastuzumab) and docetaxel in people who have HER2-positive breast cancer that has spread to different parts of the body (metastatic) and who have not received anti-HER2 therapy or chemotherapy for metastatic breast cancer.

Important Safety Information

Side effects with Perjeta

Not all people have serious side effects; however, side effects with Perjeta therapy are common. It is important for patients to know what side effects may happen and what symptoms patients should watch for.
A patient’s doctor may stop treatment if serious side effects happen. Patients should be sure to contact their healthcare team right away if they have questions or are worried about any side effects.
Most serious side effects of Perjeta

Perjeta may cause heart problems, including those without symptoms (such as reduced heart function) and those with symptoms (such as congestive heart failure).

A patient’s doctor may run tests to monitor the patient’s heart function before and during treatment with Perjeta.
Based on test results, a patient’s doctor may hold or discontinue treatment with Perjeta.
Patients should contact a health care professional immediately for any of the following: new onset or worsening shortness of breath, cough, swelling of the ankles/legs, swelling of the face, palpitations, weight gain of more than five pounds in 24 hours, dizziness or loss of consciousness.
Receiving Perjeta during pregnancy can result in the death of an unborn baby and birth defects.

Birth control should be used while receiving Perjeta and for seven months after a patient’s last dose of Perjeta. If a patient is a mother who is breastfeeding, she should talk with her doctor about either stopping breastfeeding or stopping Perjeta.
If a patient thinks she may be pregnant, she should contact her healthcare provider immediately.
If a patient is exposed to Perjeta during pregnancy or becomes pregnant while receiving Perjeta or within seven months following her last dose of Perjeta in combination with Herceptin, she is encouraged to report Perjeta exposure to Genentech at (888) 835-2555.
Other possible serious side effects

Perjeta should not be used in patients who are allergic to pertuzumab or to any of the ingredients in Perjeta.
Infusion-related reactions: Perjeta is a medicine that is delivered into a vein through a needle. Perjeta has been associated with infusion-related reactions, some fatal. The most common infusion-related reactions when receiving Perjeta, Herceptin and docetaxel were feeling tired, abnormal or altered taste, allergic reactions, muscle pain and vomiting. The most common infusion-related reactions when receiving Perjeta alone were fever, chills, feeling tired, headache, weakness, allergic reactions and vomiting.
Severe allergic reactions: Some people receiving Perjeta may have severe allergic reactions, called hypersensitivity reactions or anaphylaxis, which may happen quickly and may affect many areas of the body. Severe allergic reactions, some fatal, have been observed in patients treated with Perjeta.
Most common side effects

The most common side effects of Perjeta when given with Herceptin and chemotherapy as part of an early breast cancer regimen before surgery are:

Constipation
Damage to the nerves (numbness, tingling, pain in hands/feet)
Diarrhea
Feeling tired
Hair loss
Headache
Low levels of red blood cells
Low levels of white blood cells with or without fever
Low platelet count
Mouth blisters or sores
Nausea
Pain in the muscles
Vomiting
Weakness
Side effects may vary based on chemotherapy regimen.

The most common side effects of Perjeta when given with Herceptin and chemotherapy as part of an early breast cancer regimen after surgery are:

Diarrhea
Nausea
Hair loss
Feeling tired
Damage to the nerves (numbness, tingling, pain in hands/feet)
Vomiting
The most common side effects of Perjeta when given with Herceptin and docetaxel for treatment of breast cancer that has spread to other parts of the body (metastatic) are:

Diarrhea
Hair loss
Low levels of white blood cells with or without fever
Nausea
Feeling tired
Rash
Damage to the nerves (numbness, tingling, pain in hands/feet)
Patients are encouraged to report side effects to Genentech and the FDA. Report side effects to the FDA at (800) FDA-1088 or View Source Report side effects to Genentech at (888) 835-2555.

Patients should talk to a healthcare professional for more information about the benefits and risks of Perjeta.

Please see the Perjeta full Prescribing Information for additional Important Safety Information, including most serious side effects, at View Source

Herceptin Indication Statements

Adjuvant Breast Cancer

Herceptin is approved for the treatment of early-stage breast cancer that is Human Epidermal growth factor Receptor 2-positive (HER2+) and has spread into the lymph nodes or is HER2-positive and has not spread into the lymph nodes. If it has not spread into the lymph nodes, the cancer needs to be estrogen receptor/progesterone receptor (ER/PR)-negative or have one high-risk feature.* Herceptin can be used in several different ways:

As part of a treatment course including the chemotherapy drugs doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel. This treatment course is known as "AC→TH."
With the chemotherapy drugs docetaxel and carboplatin. This treatment course is known as "TCH."
Alone after treatment with multiple other therapies, including an anthracycline (doxorubicin)-based therapy (a type of chemotherapy).
Patients are selected for therapy based on an FDA-approved test for Herceptin.

*High risk is defined as ER/PR-positive with one of the following features: tumor size greater than 2 cm, age less than 35 years, or tumor grade 2 or 3.

Metastatic Breast Cancer

Herceptin has two approved uses in metastatic breast cancer:

Herceptin in combination with the chemotherapy drug paclitaxel is approved for the first-line treatment of Human Epidermal growth factor Receptor 2-positive (HER2+) metastatic breast cancer.
Herceptin alone is approved for the treatment of HER2-positive breast cancer in patients who have received one or more chemotherapy courses for metastatic disease.
Patients are selected for therapy based on an FDA-approved test for Herceptin.

Important Safety Information

Possible serious side effects with Herceptin

Not all people have serious side effects, but side effects with Herceptin therapy are common.

Although some people may have a life-threatening side effect, most do not.

A patient’s doctor will stop treatment if any serious side effects occur.

Herceptin is not for everyone. A patient should be sure to contact their doctor if they are experiencing any of the following:

HEART PROBLEMS

These include heart problems—such as congestive heart failure or reduced heart function—with or without symptoms. The risk for and seriousness of these heart problems were highest in people who received both Herceptin and a certain type of chemotherapy (anthracycline). In a study of adjuvant (early) breast cancer, one patient died of significantly weakened heart muscle. A patient’s doctor will check for signs of heart problems before, during, and after treatment with Herceptin.

INFUSION REACTIONS, including:

Fever and chills
Feeling sick to your stomach (nausea)
Throwing up (vomiting)
Pain (in some cases at tumor sites)
Headache
Dizziness
Shortness of breath
These signs usually happen within 24 hours after receiving Herceptin.

A patient should be sure to contact their doctor if they:

Are a woman who could become pregnant, or may be pregnant

Herceptin may result in the death of an unborn baby or birth defects. Contraception should be used while receiving Herceptin and for seven months after a patient’s last dose of Herceptin. If a patient is or becomes pregnant while receiving Herceptin or within seven months after their last dose of Herceptin, the patient should immediately report Herceptin exposure to Genentech at (888) 835-2555.

Have any signs of SEVERE LUNG PROBLEMS, including:

Severe shortness of breath
Fluid in or around the lungs
Weakening of the valve between the heart and the lungs
Not enough oxygen in the body
Swelling of the lungs
Scarring of the lungs
A patient’s doctor may check for signs of severe lung problems when he or she examines the patient.

Have LOW WHITE BLOOD CELL COUNTS

Low white blood cell counts can be life threatening. Low white blood cell counts were seen more often in patients receiving Herceptin plus chemotherapy than in patients receiving chemotherapy alone.

A patient’s doctor may check for signs of low white blood cell counts when he or she examines the patient.

Side effects seen most often with Herceptin

Some patients receiving Herceptin for breast cancer had the following side effects:

Fever
Feeling sick to your stomach (nausea)
Throwing up (vomiting)
Infusion reactions
Diarrhea
Infections
Increased cough
Headache
Feeling tired
Shortness of breath
Rash
Low white and red blood cell counts
Muscle pain
A patient should contact their doctor immediately if they have any of the side effects listed above.

Patients are encouraged to report side effects to Genentech and the FDA. Report side effects to the FDA at (800) FDA-1088 or View Source Report side effects to Genentech at (888) 835-2555.

Patients should talk to a healthcare professional for more information about the benefits and risks of Herceptin.

Please see the Herceptin full Prescribing Information for additional Important Safety Information, including most serious side effects, at View Source

About Genentech in breast cancer

Genentech has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with companion diagnostic tests, have substantially improved outcomes for HER2-positive breast cancer. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for other subtypes of the disease, including triple-negative and hormone receptor-positive.

On December 12, 2019 Zhejiang Medicine, NovoCodex and Ambrx reported positive interim topline data from the ongoing "111" trial (CTR20171162) evaluating ARX788, a novel anti-HER2 ADC, in heavily pretreated patients with metastatic HER2 positive breast cancer (Press release, Zhejiang Medicine, DEC 12, 2019, View Source [SID1234552312]). All patients enrolled had failed prior therapy with trastuzumab and 47% had failed therapy with trastuzumab and lapatinib.

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ARX788 was well tolerated at all dose levels with just two ≥ Grade 3 drug related reversible adverse events observed amongst 51 enrolled patients. ARX788 showed an excellent safety profile with dose escalation continuing. No DLT or MTD was observed as of the November 20, 2019 cut-off date.

Response rates correlated with increased dose levels. As of the cut-off date, the highest dose tested was 1.5mg/kg every three weeks. This cohort, which continues dosing and remains under observation, had already achieved a 63% overall response rate. Prior cohorts at 0.88, 1.1 and 1.3 mg/kg demonstrated overall response rates of 14%, 36% and 56% respectively. Further, the substantial increases in efficacy observed at higher doses was achieved with only mild increases in toxicity.

These data originate from the Fudan University Shanghai Cancer Center in China and are part of a broader global ARX788 development program (NCT03255070 and CTR20171162) that includes clinical sites in China, USA and Australia.

The 42nd Annual San Antonio Breast Cancer Symposium Poster is available at www.ambrx.com

Zhejiang Medicine licensed the commercial rights to ARX788 in China in 2013. The promising clinical data for ARX788 serves as a solid foundation to the second and more recent collaboration. Earlier this year, Ambrx and Zhejiang Medicine (via its subsidiary NovoCodex) entered into their second collaboration to develop and commercialize ARX305 in China. ARX305 is an anti-CD70 Antibody Drug Conjugate for the potential treatment of Renal Cell Carcinoma, Multiple Myeloma, and other solid tumors.

About HER2-Positive Breast Cancer

Almost 300,000 new cases of HER2 positive breast cancer may be diagnosed in 2020 in the US alone (approximately 15-20% of breast cancers are HER2 positive). HER2 positive breast cancer tends to be aggressive and more likely to recur than HER2 negative. There are currently no approved therapies demonstrating progression-free survival or overall survival benefit for the treatment of patients with HER2 positive metastatic breast cancer after progression on T-DM1 (which is not approved in China).