On January 5, 2017 Avidity Biosciences reported the completion of a $16 million Series B financing round to support the development of its Antibody-siRNA Conjugate (ASC) platform (Press release, Avidity Biosciences, JAN 5, 2017, View Source [SID1234521096]). The Series B round includes investment of $10 million in new capital and conversion of $6 million in convertible debt. Takeda Pharmaceuticals, through its venture group, led the Series B round, and both new and existing investors participated, including Alethea Capital, Alexandria Real Estate Equities, Brace Pharma, EcoR1 Capital, F-Prime Capital, Moore Venture Partners and Tavistock Life Sciences.

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"Our ASC platform unites two of the most impactful innovations over the past twenty years – monoclonal antibodies and oligonucleotides – to create a new class of precision medicines," said Troy Wilson, Ph.D., J.D., president and chief executive officer of Avidity Biosciences. "Although siRNA-based therapeutics have demonstrated significant clinical and commercial promise, conventional approaches are limited to targeting diseases of the liver. Because ASCs use antibodies to overcome barriers of delivering siRNA, they have the potential to impact a broader range of therapeutic areas. Our goal is to partner with leading pharmaceutical and biotechnology companies to deliver a pipeline of ASCs targeting genetic drivers of disease."

ASCs link a monoclonal antibody—designed against a specific molecular target—with a siRNA therapeutic payload, allowing the conjugate to have unmatched specificity and selectivity. In preclinical models, ASCs have shown potential to knockdown messenger RNA levels in multiple important cell types and tissues, including tumor, muscle, heart, lung, liver and B cells. In addition, ASCs have drug-like properties comparable to antibodies and antibody-drug conjugates.

In connection with the financing, Avidity Biosciences annouced that Michael Martin, Ph.D., global head of Takeda Ventures Inc., and Todd Brady, director of finance and investments of Brace Pharma Capital, will join its board of directors. Tony Hsu, founder and chief investment officer of Alethea Capital, will also join the board as a non-voting member.

"We believe Avidity’s ASC platform offers a compelling approach that builds on successes with antibodies, ADCs and oligonucleotide-based therapeutics," said Dr. Martin. "Avidity has recruited a top-notch team and made significant progress against its scientific and business goals. We look forward to working with the company to realize the promise of ASCs as a new class of precision medicines."

On January 5, 2017 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical-stage company focused on discovering and developing novel anti-cancer stem cell and immuno-oncology therapeutics, rreported its 2016 year-end cash balance and reviewed key anticipated events for 2017 (Press release, OncoMed, JAN 5, 2017, View Source [SID1234517304]).

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OncoMed ended 2016 with approximately $184.6 million in cash. OncoMed’s current cash is estimated to be sufficient to fund operations through at least the third quarter of 2018, without taking into account future potential milestone payments from partners. Full-year cash expenses for 2016 were approximately $115 million, in accordance with the company’s 2016 guidance. OncoMed expects 2017 operating cash burn to be less than $100 million, before considering potential milestones/opt-ins.

"2017 represents a potentially transformational year for our company," said Paul J. Hastings, OncoMed’s Chairman and Chief Executive Officer. "Phase 2 clinical trial results for demcizumab and tarextumab are anticipated in the first half of the year, and together those investigational drugs will be eligible for potential partner opt-ins totaling close to $100 million. Three additional programs, vantictumab, ipafricept and anti-RSPO3, are also eligible for potential partner opt-ins this year, and OncoMed could receive more than $170 million in total 2017 partner opt-in payments. At the same time, our earlier-stage programs are making progress in the clinic, we will be reporting on that progress, our two novel immuno-oncology candidates, anti-TIGIT and GITRL-Fc trimer are advancing into the clinic, and we continue to discover and develop additional novel agents directed at new immuno-oncology targets."

End-of-Year Accomplishments

In December 2016, OncoMed achieved the following:

Filed an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) for anti-TIGIT (previously "I/O#2"). TIGIT (T cell immunoglobulin and ITIM domain protein) is an inhibitory receptor that stops T-cells from attacking tumor cells. Anti-TIGIT is part of OncoMed’s collaboration with Celgene Corporation.

Enrolled the first patient in a Phase 1b clinical trial of anti-DLL4/VEGF bispecific antibody (OMP-305B83) plus FOLFIRI (folinic acid, fluorouracil and irinotecan) chemotherapy for the treatment of second-line metastatic colorectal cancer. The anti-DLL4/VEGF bispecific antibody is part of OncoMed’s collaboration with Celgene.
2017: Anticipated Key Financial Milestones and Pipeline Progress by Program

Demcizumab (anti-DLL4, OMP-21M18)

Report top-line results in the first half of 2017 from the Phase 2 YOSEMITE clinical trial of demcizumab in combination with Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine for the treatment of first-line metastatic pancreatic cancer.
OncoMed anticipates that the top-line data will include response rate, progression-free survival (PFS), interim overall survival (OS) and safety results. Subsequent analyses of event-driven OS data will be conducted mid-year and at year-end.

Submit demcizumab Phase 2 data package in the first half of 2017 to Celgene for opt-in consideration.
The Phase 2 YOSEMITE PFS, interim OS, response rate, and exploratory biomarker data are expected to form the basis of a demcizumab data package. In the first half of 2017, OncoMed will also provide Celgene with response, PFS and safety data from the Phase 2 DENALI clinical trial of demcizumab plus carboplatin and pemetrexed in first-line non-small cell lung cancer (NSCLC), as well as interim safety and efficacy data from the ongoing Phase 1b clinical trial of demcizumab plus pembrolizumab (anti-PD1, Keytruda). Additional data analyses for each of these studies will be conducted as each trial matures, with planned and final analysis of OS from the DENALI trial at year-end.
OncoMed will be entitled to a $70 million opt-in payment if Celgene exercises its option on demcizumab. Following option exercise, OncoMed and Celgene will co-develop and co-commercialize demcizumab in the U.S., sharing profits 50/50, while Celgene will lead development and commercialization outside the U.S.

Complete enrollment in the Phase 1b demcizumab plus pembrolizumab clinical trial.

Present interim data from the Phase 2 YOSEMITE and the Phase 1b demcizumab plus pembrolizumab dose-escalating trial and expansion arms at medical oncology meetings during the second half of 2017, pending abstract acceptance.
Tarextumab (anti-Notch 2/3, OMP-59R5)

Report top-line progression-free survival, overall survival, and biomarker-driven efficacy data in the first half of 2017 from the Phase 2 PINNACLE clinical trial of tarextumab in combination with cisplatin/carboplatin and etoposide for the treatment of first-line small cell lung cancer (SCLC).

Submit a tarextumab data package in the first half of 2017 to GlaxoSmithKline (GSK). GSK then has the opportunity to review the data package and consider exercising its option.
If GSK exercises its option on tarextumab, OncoMed would be entitled to receive a $25 million payment. GSK would then lead and fully fund further development and commercialization.

Present data from the Phase 2 PINNACLE clinical trial at a medical oncology meeting during the second half of 2017, pending abstract acceptance.
Wnt programs — Vantictumab (anti-Fzd7, OMP-18R5) and Ipafricept (Fzd8-Fc, OMP-54F28)

Submit data package for both programs in the first half of 2017 to Bayer for opt-in consideration.
Data package will include Phase 1b clinical trial data from the ongoing studies of both vantictumab and ipafricept.
OncoMed will be entitled to receive a $25 million payment for vantictumab and a $15 million payment for ipafricept if Bayer exercises its options on the investigational drugs. Upon option exercise, Bayer will lead and fully fund further development and commercialization.

Present Phase 1b data from the ongoing clinical trials at medical oncology meetings during 2017, pending abstract acceptance.
Anti-RSPO3 (OMP-131R10)

Continue enrollment in the Phase 1a biomarker-selected expansion cohort of the Phase 1a clinical trial and the Phase 1b trial of anti-RSPO3 in combination with FOLFIRI chemotherapy in patients with colorectal cancer, including biomarker-positive subjects.

Submit a data package upon the achievement of certain enrollment objectives to Celgene for opt-in consideration.
OncoMed will be entitled to receive a $37.75 million payment if Celgene exercises its option on anti-RSPO3. Upon option exercise, OncoMed and Celgene would co-develop and co-commercialize anti-RSPO3 in the U.S., sharing profits 50/50, while Celgene would lead development and commercialization outside the U.S.
Anti-DLL4/VEGF bispecific (OMP-305B83)

Initiate second Phase 1b clinical trial of the anti-DLL4/VEGF bispecific antibody in combination with paclitaxel for the treatment of platinum-resistant ovarian cancer.
Brontictuzumab (anti-Notch1, OMP-52M51)

Begin patient enrollment in the first half of 2017 of planned Phase 1b clinical trial of brontictuzumab combined with trifluridine and tipiracil tablets (Lonsurf) in third-line colorectal cancer. The trial includes enrollment of biomarker-positive patients whose tumors express the activated form of Notch1.
Immuno-oncology Pipeline

Initiate Phase 1 clinical trial in the first half of 2017 of anti-TIGIT (OMP-313M32).
Celgene will have an option to license anti-TIGIT at the end of the Phase 1a clinical trial.

File an IND in the first half of 2017 for OncoMed’s wholly owned GITRL-Fc (OMP-336B11) trimer program.

Present preclinical data related to anti-TIGIT, pending abstract acceptance.
In future years, OncoMed is eligible for more than $4 billion in total potential milestone and option payments from its partners under its collaboration agreements with Celgene, Bayer, and GSK. To date, OncoMed has received over $465 million from its existing partners.

On January 5, 2017 Dynavax Technologies Corporation (NASDAQ: DVAX), a clinical-stage biopharmaceutical company, reported that it is reshaping its strategy and operations to prioritize its emerging clinical and preclinical immuno-oncology portfolio (Press release, Dynavax Technologies, JAN 5, 2017, View Source [SID1234517380]). The company has implemented significant organizational restructuring and cost reductions to align around its immuno-oncology business, while allowing it to advance HEPLISAV-B [Hepatitis B Vaccine, Recombinant (Adjuvanted)], its investigational hepatitis B vaccine candidate, through the U.S. Food and Drug Administration (FDA) review process and an approval decision. Dynavax continues to believe that HEPLISAV-B is an approvable product and plans to submit its response to the FDA’s outstanding questions shortly.

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To achieve these savings, Dynavax has suspended manufacturing for HEPLISAV-B and reduced its global workforce by 38 percent. The company will incur restructuring costs, currently estimated to be $3.0 million, primarily in the first quarter of 2017. The company estimates that its cash, cash equivalents and marketable securities were approximately $81.4 million as of December 31, 2016. Going forward, it expects HEPLISAV-B costs prior to any FDA decision to be less than $1 million per month, and all other operating costs to be less than $60 million per year to support continued development of its oncology program. This restructuring is currently estimated to result in approximately a 40 percent reduction in cash burn. The company will continue to evaluate the possibility of a partnership to support HEPLISAV-B as it increasingly concentrates its own strategic focus on oncology.

"We value all of our colleagues, so reducing our workforce is a sad and difficult decision. But it is one we believe is necessary to align our organization to reflect that of a clinical R&D-stage company with a promising immuno-oncology pipeline, which has become a strategically important area of our business and one we believe can potentially benefit thousands of people with cancer," said Eddie Gray, chief executive officer of Dynavax. "These measures will increase our financial strength and position us well to create significant long-term clinical and financial value. They also will allow us to advance HEPLISAV-B toward approval while we continue to evaluate the possibility of a partnership to support its approval and launch. We are grateful to all affected employees for their dedication to bringing us this far."

Prioritizing Diversified Immuno-Oncology Pipeline
Dynavax has made notable progress in the rapidly advancing area of immuno-oncology, and is focusing on two promising compounds that have shown potential to enhance the immune response against cancer.

The company’s lead clinical candidate, SD-101, an investigational cancer immunotherapeutic, is currently being studied in several Phase 1/2 studies evaluating its potential to be broadly effective against multiple solid tumors and hematologic malignancies. SD-101, an intratumoral TLR9 agonist, has shown encouraging early clinical data in metastatic melanoma.

At the Society for Melanoma Research conference in November 2016, Dynavax announced the first findings from an ongoing Phase 1/2 study of SD-101 in combination with Keytruda (pembrolizumab), Merck’s anti-PD-1 treatment. Early results evaluating 13 patients with metastatic melanoma for efficacy and 19 patients for safety were reported. In patients naïve to anti-PD-1 treatment, objective responses were observed in four of five patients (80 percent), including one complete response and three partial responses. In a small number of patients with progressive disease stable disease was observed while receiving Keytruda and SD-101 in combination. The combination of the two drugs was well-tolerated with no dose-limiting toxicities. These encouraging clinical data will be enhanced by a dose-expansion phase to further explore the efficacy of this combination.

Dynavax is also developing a second TLR9 agonist, DV281, which has completed preclinical testing in models for lung cancer. Lung cancer remains an area of high unmet need, with fewer than 20 percent of patients responding to the most recently-approved immunotherapies. DV281 will be administered as an inhaled therapeutic. Dynavax intends to begin Phase 1 studies of DV281 in the second quarter of 2017.

The company expects to present additional data from its immuno-oncology portfolio at medical conferences throughout 2017, including at the American Association for Cancer Research (AACR) (Free AACR Whitepaper), the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper).

Continuing to Advance HEPLISAV-B while Maintaining Manufacturing Capacity at Reduced Cost
Dynavax plans to respond this month to the November 2016 Complete Response Letter (CRL) from the FDA regarding its Biologics License Application (BLA) for HEPLISAV-B, and will advance the vaccine through an expected six-month FDA review period. The company remains confident that the existing clinical data package meets the requirements for approval. During the regulatory review period, Dynavax will retain, but furlough, the majority of the workforce supporting its manufacturing facility in Germany. This approach will enable the company to leverage the existing stockpiled inventory of HEPLISAV-B, while providing it with the ability to re-activate and scale for commercial launch activities.

Conference Call Details
The Dynavax management team will host a conference call and webcast today, Thursday, January 5, 2017, at 4:30 p.m. Eastern Time, to provide more information about the restructuring. The live call can be accessed by phone by dialing (877) 479-1857 (domestic) or +1 (503) 343-6309 (international) and specifying conference call code 47911578. A link to the live webcast may be accessed by visiting the "Investors" section of the Dynavax website or directly at www.dynavax.com. A replay of the conference call may be accessed for one week following the call by dialing (855) 859-2056 (domestic) or +1 (404) 537-3406, and using the passcode 47911578.

About SD-101
SD-101 is Dynavax’s proprietary CpG-C class oligodeoxynucleotide. SD-101 is a potent activator of dendritic cells, activating them to mature and produce Type 1 interferons through specific binding to TLR9, a key recognition receptor in the innate immune system. SD-101 is delivered directly to the tumor, where it can stimulate highly effective immune responses to tumor antigens. SD-101 is being evaluated in several Phase 1/2 oncology studies to assess its safety and activity.

About DV281
DV281, a newly developed TLR9 agonist, is a CpG-C class oligodeoxynucleotide developed specifically for inhaled delivery to lung tumors that are not easily accessible for intratumoral injection. Inhaled DV281 induces dendritic cell activation and tumor microenvironment changes comparable to intratumoral injection of SD-101. Studies in animal models of lung tumors show that DV281 dramatically reduces lung tumor burden and leads to immune-mediated control of tumor metastases outside the lung. Dynavax intends to initiate a Phase 1 study in the second quarter of 2017.

About HEPLISAV-B
HEPLISAV-B is an investigational adult hepatitis B vaccine that combines hepatitis B surface antigen with Dynavax’s proprietary TLR 9 agonist to enhance the immune response. HEPLISAV-B is administered in two doses over one month. In Phase 3 trials, HEPLISAV-B demonstrated higher and earlier protection with fewer doses than a currently licensed hepatitis B vaccine. The investigational vaccine’s safety profile is based on clinical trials that generated safety data from more than 14,000 participants. The most frequently reported local reaction was injection site pain. The most common systemic reactions were fatigue, headache and malaise, all of which were similar to an existing vaccine.

Dynavax has worldwide commercial rights to HEPLISAV-B.

On January 4, 2017 Bavarian Nordic A/S (OMX: BAVA, OTC: BVNRY) reported guidance for the current estimated timing of interim and final overall survival analysis from the PROSPECT study – a placebo controlled Phase 3 study designed to investigate the efficacy of PROSTVAC to prolong the survival of men with metastatic castration-resistant prostate cancer (mCRPC) (Press release, Bavarian Nordic, JAN 4, 2017, View Source [SID1234517268]).

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The company maintains its previous guidance that full data is expected within this year, albeit in the second half of 2017, with the third interim analysis likely to occur around mid-2017. This estimate is based on a decline in the number of average monthly events currently seen in the PROSPECT study.

"As there has been speculation that the third interim could occur during first quarter of 2017, we believe it is important to update the market on the current estimated timelines for readout of the Phase 3 study" said Paul Chaplin, President and CEO of Bavarian Nordic.

While the company remains blinded to all patient specific data, the latest estimates have been provided by the independent Data Monitoring Committee (DMC) following a routine analysis of the current survival data.

"While we will have to await the final read out of the PROSPECT study to establish the efficacy of PROSTVAC, we are encouraged that the current monthly event rate has declined. This is great news for the patients. Not only is this consistent with an improvement in the standard of care for patients with mCRPC, which has been observed in recent years, but could also be indicative of a therapeutic effect of PROSTVAC as well" said Paul Chaplin.

About the PROSPECT study
PROSPECT is a global, randomized, double-blind, placebo-controlled phase 3 study being conducted under a Special Protocol Assessment (SPA) from the FDA. The objective of the study is to determine whether PROSTVAC alone or in combination with GM-CSF is effective in prolonging overall survival. The study has been fully enrolled with 1,297 asymptomatic or minimally symptomatic mCRPC patients as of January 2015. Patients were enrolled at more than 200 sites in 15 countries. Both the first and second interim analyses confirmed that the study would continue as planned. Final study data requires 534 events in both comparisons of treatment arms versus placebo, and the third interim analysis will occur at 427 events.

About PROSTVAC
PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec, or "rilimogene") is a prostate specific antigen (PSA)-targeted immunotherapy candidate designed to enhance or stimulate the body’s immune response, specifically T cells that will home to and kill prostate cancer cells, altering the course of the disease and improving overall survival (OS) of patients with prostate cancer. A robust data package has been established that includes 18 ongoing or completed clinical studies, comprising more than 2,000 patients of which more than 1,100 patients have been actively treated with PROSTVAC, which has been generally well-tolerated. A randomized, placebo-controlled Phase 2 trial demonstrated the potential of PROSTVAC to extend the median overall survival by 8.5 months in patients with advanced prostate cancer. These results led to the initiation of the PROSPECT pivotal Phase 3 study.

PROSTVAC is being developed in collaboration with the National Cancer Institute under a Cooperative Research and Development Agreement.

On January 4, 2017 Tarveda Therapeutics a biopharmaceutical company discovering and developing Pentarins as a new class of potent and selective anti-cancer medicines, reported that a Phase 1/2a clinical trial evaluating PEN-221 in patients with advanced neuroendocrine tumors and small cell lung cancer expressing the somatostatin receptor 2 (SSTR2) is underway, with patients enrolled and treated (Press release, Tarveda Therapeutics, JAN 4, 2017, View Source [SID1234517269]). The somatostatin receptor is highly expressed in neuroendocrine cancers. PEN-221 is a novel, miniaturized drug conjugate designed to selectively target SSTR2 and then internalize and release its potent DM1 payload in the tumor cell.

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"Pentarins are engineered to rapidly penetrate and kill solid tumors that have proven challenging for treatment modalities such as antibody drug conjugates and chemotherapeutics," said Gordon B. Mills, M.D., Ph.D., Professor and Chair, Department of Systems Biology, at The University of Texas MD Anderson Cancer Center, Houston, TX. "The miniaturized size, unique design and potent payloads of Pentarins allow for sustained payload release in solid tumors to drive potential efficacy while sparing normal tissue.

"PEN-221 has high affinity for the SSTR2 on the surface of neuroendocrine and small cell lung cancer cells, which facilitates internalization followed by release of its potent cell-killing payload, DM1. Pentarins offer a new treatment approach to address the deficits of current treatments, and PEN-221 has the potential to address the urgent and significant medical need of patients with neuroendocrine and small cell lung cancers. Having an imaging approach to identify neuroendocrine and small cell lung cancers expressing the somatostatin receptor 2 makes the PEN-221 trial an exciting proof-of-concept as well as an opportunity for patients with these challenging tumors," concluded Mills.

The Phase 1/2a first-in-human study is an open-label, multicenter trial to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of PEN-221 in patients with SSTR2-expressing advanced neuroendocrine cancers, including a range of neuroendocrine tumors and small cell lung cancer. Utilizing FDA-approved imaging diagnostics, the study employs a seamless, Phase 1/2a design that identifies and selects advanced cancer patients with SSTR2 expressing tumors. These patients are believed to be the most likely to benefit from treatment with PEN-221. For additional information on this clinical trial, please visit clinicaltrials.gov, identifier number NCT02936323.

"The initiation of this Phase 1/2a clinical trial of PEN-221 in patients with neuroendocrine tumors and small cell lung cancer marks an important milestone in the development of this product candidate and our Pentarin drug conjugates," said Leila Alland, M.D., Chief Medical Officer of Tarveda. "PEN-221 consistently demonstrated complete and durable regressions in hard-to-treat xenograft cancer models. We and our industry leading clinical investigators are excited to advance this therapy into the clinic."

About Pentarins
Tarveda is developing Pentarins, potent and selective miniaturized drug conjugates with high affinity for specific cell surface and intracellular targets. Pentarins are engineered to bind to their tumor cell targets and provide sustained release of their potent therapeutic payloads deep into solid tumor tissue. Comprised of a targeting ligand conjugated to a potent cell-killing agent through a chemical linker, Pentarins are designed to overcome the deficits of both larger antibody drug conjugates and small molecules that limit their therapeutic effectiveness against solid tumors. Together, the components of Tarveda’s Pentarins have distinct, yet synergistic, anticancer attributes: the small size of Pentarins allows for effective penetration and distribution into the tumor tissue, the ligand’s targeting ability allows for specific binding and retention in tumor cells, and the chemical linker is tuned to optimize the release of the potent, cell-killing payload inside the cancer cells for efficacy.