I-Mab, ABL Bio OKd to Start Phase 1 for Bispecific Anti-Cancer Antibody

 I-Mab (the “Company”) (Nasdaq: IMAB), a clinical-stage biopharmaceutical company committed to the development of novel biologics, and ABL Bio, Inc. (Kosdaq:298380, hereafter “ABL”), a South Korean biotech specializing in bispecific antibody technology, jointly announced that the U.S. Food and Drug Administration (FDA) has approved the Investigational New Drug (IND) application for initiating phase 1 trial for bispecific antibody TJ-CD4B/ABL111. The phase 1 clinical trial will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of TJ-CD4B/ABL111 in advanced or metastatic solid tumors.

TJ-CD4B/ABL111 is a novel bispecific antibody that works through binding to a tumor antigen Claudin 18.2 (CLDN18.2) which is selectively expressed in several cancers and to 4-1BB, a co-stimulatory molecule expressed on T cells, to activate immune response within tumor for better anti-tumor activity. Preclinical studies demonstrate that TJ-CD4B/ABL111 has superior anti-tumor property as compared to the two monoclonal antibodies when acting alone or in combination. This superior anti-tumor activity is achieved locally on tumor site, thus minimizing the risk of liver and systemic side effects commonly associated with 4-1BB antibody when used alone.

https://finance.yahoo.com/news/mab-abl-bio-receive-us-120000865.html

Ascendis downgraded at Oppenheimer

To Perform from Outperform.

https://finviz.com/quote.ashx?t=ASND&ty=c&ta=1&p=d 

Ionis' antisense drug curbs HAE attacks in phase 2

 People with hereditary angioedema (HAE) suffer recurrent attacks, including swelling of the airways or intestinal tract that can be life-threatening. Ionis Therapeutics’ antisense treatment beat placebo at curbing those attacks in a phase 2 study, reducing the number of attacks patients experienced per month by an average of 90%, top-line data show.

The phase 2 study tested the drug, IONIS-PKK-LRx, against placebo in 20 patients with Type 1 or Type 2 HAE, both of which are caused by mutations in the C1NH gene that lead to deficiency of a plasma protein called C1-esterase inhibitor. People with HAE suffer sudden attacks of rapid swelling, known as edema, in the feet, limbs and face as well as in the airways and intestinal tract.

Of the 20 patients, 14 received the drug and six got placebo injected just under the skin once a month. The data come from weeks 5 through 17 of treatment. During that time frame, the drug cut the number of monthly HAE attacks by an average of 90%.

For most of the treated patients (92%), that meant having no attacks at all during that time, compared to none of the placebo patients, the company said in a statement. Ionis plans to present full data at a medical meeting later this year.

Most of the side effects were mild, affecting the treatment and placebo groups at similar rates, the company said. The most common side effects were headache and nausea, both of which turned up more frequently in the placebo group.

IONIS-PKK-LRx works by reducing the production of prekallikrein, or PKK, an enzyme that activates kinins, proteins that cause inflammation. Several drugs have been approved to treat HAE, including CSL’s Haegarda and Shire’s Cinryze, both of which boost C1-esterase inhibitor activity. Takeda markets a pair of HAE drugs picked up in its Shire buyout: Firazyr, approved in 2011, treats all kinds of HAE by targeting the bradykinin B2 receptor, and Takhzyro, OK’d in 2019, targets the kallikrein enzyme.

Approved HAE drugs are given by injection or intravenous infusion, so some companies are working on oral drugs for HAE. Pharvaris is developing a treatment that hits the same target as Firazyr, while Attune Pharmaceuticals is working on an oral kallikrein inhibitor. BioMarin, on the other hand, is taking a gene therapy approach.

https://www.fiercebiotech.com/biotech/ionis-antisense-drug-curbs-hae-attacks-phase-2

Novartis expands targeted radioligand therapy pipeline with in-license

 Novartis has obtained exclusive worldwide

rights to develop and commercialize therapeutic applications for a 
library of Fibroblast Activation Protein (FAP) targeting agents 
including FAPI-46 and FAPI-74, through an assignment agreement with 
iTheranostics, Inc., an affiliate of SOFIE Biosciences, Inc. The FAP 
assets were originally developed at the University of Heidelberg. The 
agreement also includes co-exclusive rights for Novartis to develop 
imaging applications for these assets. 
 
   Fibroblast activation protein (FAP) is a cell-surface protein expressed 
at low levels in most normal adult tissues, but over-expressed in common 
cancers, particularly on cancer-associated fibroblasts that form the 
tumor stroma, which is essential for growth(1) (,2) (,3) (,4) . High FAP 
expression on cancer-associated fibroblasts is generally associated with 
worse prognosis in solid tumors due to promotion of tumorigenesis and 
progression(4) (,5) (,6) (,7) . 
 
   "We continue to invest in radioligand therapy as one of the four unique 
platforms of Novartis Oncology. We believe working across multiple 
approaches is the key to reimagining cancer care," said Susanne 
Schaffert, PhD, President, Novartis Oncology. "FAP is an exciting target 
and these agents are a great fit with our radioligand therapy pipeline, 
which we are actively investigating across multiple tumor types. We 
believe this technology has the potential to transform many patients' 
lives." 
 
   Targeted radioligand therapy is a type of precision medicine combining 
two key elements: a targeting compound, or ligand, and a radioactive 
isotope, causing DNA damage that inhibits tumor growth and replication. 
These targeted drugs bind to markers or proteins over-expressed by 
certain tumors, or tumor-associated tissue, such as stroma. Due to the 
high-affinity of these agents for specific tumor cells or associated 
tumor tissue, surrounding healthy tissue is less affected. 

https://www.marketscreener.com/quote/stock/NOVARTIS-AG-9364983/news/Press-Release-nbsp-Novartis-expands-targeted-radioligand-therapy-pipeline-with-in-license-for-comp-32833355/

Asian countries scramble for vaccine supplies after India export curbs

 Several Asian countries scrambled to find alternative sources for COVID-19 inoculations on Tuesday after export restrictions by manufacturer India left a World Health Organization-backed global vaccine sharing programme short of supplies.

South Korea, Indonesia and the Philippines are among countries to be hit by shipment delays to vaccines they have been promised under the COVAX programme, which was created mainly to ensure supplies for poorer countries.

“Our planned increase in daily vaccinations will be affected,” Carlito Galvez, Philippines’ vaccination chief, told reporters.

India, the world’s biggest vaccine maker, put a temporary hold on exports of AstraZeneca’s vaccine being manufactured by the Serum Institute of India (SII), as officials focus on meeting rising domestic demand.

The Serum Insitute was due to deliver 90 million vaccine doses to COVAX over March and April and, while it was not immediately clear how many would be diverted for domestic use, programme facilitators warned that shipment delays were inevitable.

South Korea confirmed it would only receive 432,000 doses of the 690,000 it had been promised and delivery of those would be delayed until around the third week of April.

“There’s uncertainty over global vaccine supplies but we’re working on a plan to ensure no disruptions in the second quarter and making efforts to secure more vaccines,” Kim Ki-nam, head of South Korea’s COVID-19 vaccination task force team. Officials said they were in talks with AstraZeneca to accelerate shipments procured through a separate deal.

Philippines President Rodrigo Duterte loosened government restrictions on private sector imports of vaccines, pleading with companies to obtain supplies no matter the cost, as his country battles a resurgence of the pandemic.

In Vietnam, officials have similarly asked the private sector to step in after their COVAX supplies were slashed by 40% to 811,200 doses and shipments were pushed back by weeks.

In Indonesia, health ministry official Siti Nadia Tarmizi told Reuters that 10.3 million doses from COVAX were likely delayed until May.

India has not provided details on the length of its export curb but UNICEF, a distributing partner of COVAX, said at the weekend that deliveries are expected to resume by May.

India’s decision is the latest in a series of setbacks for the COVAX facility, relied on by 64 poorer countries, after production glitches and a lack of funding contribution from wealthy nations.

CHINA AND RUSSIA

China and Russia are primed to step into the breach.

“We have good diplomatic relations with China and Russia and we are asking if we can have access to their vaccines in April,” the Philippines’ Galvez said.

Both the Philippines and Indonesia are currently relying heavily on vaccines from China’s Sinovac Biotech to run their inoculation drives. The Philippines and Vietnam have both approved Russia’s Sputnik V vaccine, along with more than 50 other countries, mainly developing nations. The Philippines expects to receive its first batch of Sputnik V in April.

Chinese vaccine maker Sinopharm, meanwhile, plans to produce its COVID-19 vaccine at a new plant in the United Arab Emirates.

The spate of export curbs is also being felt by wealthier countries that are reliant on foreign manufacturing, including Japan, where the national vaccine rollout has been slow due to the limited number of Pfizer vaccines shipped from Europe.

“Some people are using vaccines for diplomacy, some people are trying to prioritize. Some people are buying like three to five times as many vaccines compared to their population. That’s unnecessary,” Japan’s vaccine minister, Taro Kono, told Reuters on Monday in an interview.

“We really need to have the global leaders sit down and think this is a global issue, not the domestic issue, and try to solve this together.”

https://www.reuters.com/article/us-health-coronavirus-covax-impact/asian-countries-scramble-for-vaccine-supplies-after-india-export-curbs-idUSKBN2BM0JS

Tiziana Plans Phase 2 Antibody Study in Moderate to Severe Covid-19

 

• Since the anti-inflammatory effect of the nasally administered Foralumab is through the modulation of the immune system and not by directly targeting Covid-19, this therapeutic approach could be useful for newly identified Covid-19 variants in the UK, South Africa and Brazil.
• Foralumab is the first monoclonal antibody that can be dosed nasally or orally, due to its ability to effect systemic immunity via the epithelial lining of the nose, respiratory tract and gut.
• The direct rapid delivery of Foralumab to the nasal passage and respiratory tract was shown in a previous study of mild to moderate Covid-19 patients to suppress lung inflammation, as evident from CT scans and reduced systemic markers of inflammation including interleukin-6 and C-reactive protein.

https://www.biospace.com/article/releases/tiziana-plans-phase-2-clinical-study-in-moderate-to-severe-covid-19-patients-with-nasal-administration-of-foralumab-a-fully-human-anti-cd3-monoclonal-antibody/

Would suspending covid vax patents do anything to up supply of doses?

 Some lawmakers are calling on the Biden administration to suspend patent protections on COVID-19 vaccines to help boost supply in other countries. And last week, they took a shot at pitching the idea to White House officials.

After House Speaker Nancy Pelosi sent a request to review proposals for breaking COVID-19 drug and vaccine patents, the White House held a meeting last week, CNBC reports, citing people familiar with the situation.

The prevailing view among supporters is that “we’re not safe until the world is safe," one source told CNBC. The United States has administered more than 143 million coronavirus vaccine doses, while some countries have yet to start vaccinations.  

The lawmakers aren't the only ones questioning the effect of COVID-19 drug and vaccine patents on global supply. The talks come as Moderna faces renewed pressure to share its shot, and last month, Doctors Without Borders urged wealthy countries not to oppose a proposed intellectual property waiver at the World Trade Organization that would allow countries to ignore patents until the world reaches herd immunity.

Meanwhile, companies such as AstraZeneca and Novavax have inked large deals to allow their vaccine doses to make their way to countries worldwide.

It’s unclear whether the Biden team will move forward, and plenty of questions remain. For one, it’s not clear how the U.S. would boost access elsewhere simply by suspending intellectual property protections on COVID-19 drugs and vaccines. Some influential experts argue that seizing patents isn’t a realistic solution. 

A spokesman for the Office of the U.S. Trade Representative told CNBC the agency is “evaluating the efficacy of this specific proposal by its true potential to save lives." 

In a Wall Street Journal op-ed, former FDA commissioner Scott Gottlieb noted that manufacturing COVID-19 vaccines is complex and requires materials that are in very high demand.  

“Allowing other manufacturers to appropriate the intellectual property wouldn’t increase the supply of the starting ingredients,” Gottlieb wrote. “It will make it harder for the current drugmakers to produce these vaccines.” 

Under the proposal, worldwide COVID-19 vaccine production would decline, not increase, Gottlieb argued.

Instead, he recommends the Biden team look to the George W. Bush administration's AIDS response. Under the President’s Emergency Plan for AIDS Relief, or Pepfar, the U.S. government teamed with drugmakers to purchase and distribute trusted AIDS drugs in Africa, Gottlieb wrote. 

In response to the global COVID-19 crisis, the government could boost manufacturing capacity by helping to produce raw materials and purchasing specialized equipment, Gottlieb wrote. Then, the U.S. could support donations of high-quality vaccines in low- and middle-income countries. 

Aside from the practical concerns are legal questions. In a November op-ed in The Hill, law professor Sean M. O’Connor wrote that patent-breaking proposals “fatally misconstrue the law.” O’Connor, who serves as executive director of the Center for the Protection of Intellectual Property at George Mason University, was writing at the time about calls to seize patents on Gilead's COVID-19 antiviral Veklury. 

Still, he argued the Biden administration would “do well to listen to experienced voices in drug development ... rather than follow these mistaken calls for seizing, breaking or bypassing drug patents.” 

For many months as the pandemic has played out, patient advocates have focused on Moderna’s intellectual property because the U.S. government was a key research partner. In a letter last week, Public Citizen, AIDS group PrEP4All and others called on the government to leverage its power on a soon-to-be-issued patent to help scale up global supply for the vaccine.

Their proposal is different from simply bypassing drug company patents. Because Moderna’s vaccine uses technology in the U.S. government patent, the advocates are calling on the government to license its tech to Moderna. Under that license, the government could require “provisions to help increase global access” rather than just a royalty. 

“This government-owned patent is an important policy tool that the U.S. government could use to facilitate scale up of production of mRNA-1273 and ensure rapid, equitable global access,” the group wrote. 

Under the license, the government could bring more manufacturing partners on board and require tech sharing with the World Health Organization to boost capacity, the group wrote. The government could also require universal pricing. 

https://www.fiercepharma.com/pharma/biden-faces-calls-to-break-covid-19-drug-and-vaccine-patents-would-boost-global-supply