Pipeline

UNMET NEED

Epstein-Barr virus (EBV) is present more than 90% of the world's population and is the leading cause of infectious mononucleosis. Beyond the acute illness, EBV remains dormant for life and is linked to several serious cancers, as well as multiple sclerosis. Despite this broad impact on human health, there are currently no approved vaccines or targeted treatments to prevent EBV infection or its long-term sequela.

SCIENTIFIC RATIONALE

EBV infects the body primarily through two cell types: B cells and epithelial cells. Four viral glycoproteins – gp350, gH, gL and gp4 – work together to open the door to both of these cell types. Our vaccine is engineered as a self-assembling nanoparticle that displays all four of these proteins in their natural shape and arrangement that trains the immune system to recognize and block the virus before it can establish infection.

ADVANTAGES

Using insights from structural biology and nanotechnology, ModeX designed its EBV vaccine to present all four viral glycoproteins in their native conformation on a symmetrical nanoparticle scaffold. This precise spatial arrangement maximizes the immune response and has been shown in animal models to generate potent neutralizing antibodies that protect against infection. 

COLLABORATION PARTNER

ModeX and Merck entered into an exclusive worldwide license and collaboration agreement for the development of MDX2201. The collaboration combines ModeX's innovative multi-targeted nanoparticle vaccine platform with Merck's world-class vaccine development and commercialization expertise. Merck is leading all clinical, regulatory and commercial activities globally, while ModeX is eligible to receive milestone payments and royalties on global sales.

UNMET NEED

Solid tumors represent the majority of cancer cases and are associated with poor long-term survival. For example, even with the most advanced immunotherapy regimens available today, fewer than 30% of lung cancer patients achieve long-term survival. A critical reason treatments fail over time is that tumors can shed or reduce the surface proteins that drugs are designed to target, a phenomenon called antigen escape, which renders initially effective therapies powerless.

SCIENTIFIC RATIONALE

MDX2001 targets two tumor antigens – cMET and Trop2 – that are highly overexpressed across multiple solid tumor types. By simultaneously engaging both targets, the drug significantly reduces the likelihood that a tumor cell can escape treatment by losing expression of just one. At the same time, MDX2001 activates T cells through CD3 and CD28 to mimic the natural two-signal process that the immune system uses to fully switch on its killer cells and drive more powerful and sustained tumor killing. 

ADVANTAGES

MDX2001 is the first tetraspecific T-cell engager to reach clinical trials. Unlike existing bispecific antibodies that target only one tumor antigen and engage T cells through a single activation signal (CD3 alone, which leads to T cell exhaustion), MDX2001 simultaneously locks onto two tumor targets and delivers dual T-cell activation. This four-pronged approach gives the immune system a stronger, longer-lasting grip on cancer while closing the escape routes that allow tumors to evade single-target therapies.

UNMET NEED

Cancer immunotherapy has transformed oncology, yet the majority of patients do not achieve a complete or lasting response. The fundamental problem is that the T cells responsible for fighting cancer often become exhausted or die before their job is done. This is especially true for patients who have already been treated with checkpoint inhibitors, today's most common immunotherapy, as tumors have learned to evade or outlast the immune response. There is a significant and growing unmet need for therapies that can reboot and sustain immune activity in treatment-resistant cancers.

SCIENTIFIC RATIONALE

Effective T-cell activation requires two simultaneous signals: CD3, which triggers the initial attack; and CD28, which keeps the T cell alive and functional. Adding a third signal, 4-1BB, further enhances the survival of stem-like T cells for a rare, highly potent immune cell subset that correlates strongly with favorable outcomes in cancer patients. MDX2004 is engineered to deliver all three signals at once, amplifying and sustaining the immune response in ways that single-signal approaches simply cannot achieve.

ADVANTAGES

MDX2004 is a novel trispecific antibody-fusion protein that takes a fundamentally different approach to immunotherapy and targets CD3, CD28 and 4-1BB (CD137) on human T cells. Rather than releasing brakes on the immune system as checkpoint inhibitors do, MDX2004 acts as a direct accelerator to simultaneously fuel T-cell activation through multiple pathways. It is the only clinical-stage drug designed to expand stem-like T cells via three co-stimulatory signals in a single molecule, which have been associated with favorable responses to immunotherapy. In addition, MDX2004 may help restore immune function in subjects with underlying immune impairment from aging, chronic infections or chemotherapies. 

UNMET NEED

B-cell blood cancers, including lymphoma and leukemia, affect hundreds of thousands of patients each year. While survival rates have improved, relapse and treatment resistance remain common. Approximately 30-40% of patients relapse or fail to respond to initial treatment. CAR-T cell therapies, used in relapsed cases, achieve complete remission in fewer than half of patients overall and are logistically difficult to manufacture and administer at scale. A significant unmet need persists for patients whose cancer has returned or stopped responding.

SCIENTIFIC RATIONALE

MDX2003 is a T-cell engager simultaneously targeting CD19 and CD20 on cancer cells, along with CD3 and CD28 on T cells. By locking onto two tumor targets at once, the drug prevents tumors from escaping by shedding one surface protein, which is a common resistance mechanism that defeats single-target bispecifics and CAR-T therapies. The dual CD3/CD28 co-stimulation simultaneously activates T cells and prolongs their survival to produce a stronger and more durable immune attack. 

ADVANTAGES

MDX2003 is the world's first tetraspecific T-cell engager and addresses the two most common reasons patients relapse after modern B-cell cancer therapy, including tumor antigen escape and T-cell exhaustion. In addition, the drug may hold promise for autoimmune diseases where B cells are the underlying culprit, such as lupus and rheumatoid arthritis.

UNMET NEED

COVID-19 continues to pose a serious health threat, particularly for immunocompromised and high-risk individuals with an estimated 15-20 million people in the U.S. alone, including the elderly, cancer patients, transplant recipients and those on immunosuppressive therapies. Earlier generations of monoclonal antibodies have lost effectiveness against currently circulating variants and highlight the limitations of first-generation approaches in the face of rapid viral evolution. There is an urgent need for durable, off-the-shelf antibody therapies that can protect vulnerable patients against current and future variants.

SCIENTIFIC RATIONALE

MDX2301 is a tetravalent bispecific antibody that incorporates two distinct binding domains to target separate sites on the SARS-CoV-2 receptor-binding domain. By occupying two distinct epitopes at once, MDX2301 raises the genetic barrier for viral escape as the virus would need to mutate multiple sites simultaneously to evade recognition.

ADVANTAGES

ModeX's proprietary MSTAR platform enables the combination of multiple antibody binding domains into a single molecule to create a drug designed from first principles to stay ahead of viral evolution. Where conventional monoclonal antibodies are rendered obsolete by each new variant, MDX2301's multi-epitope design provides inherent resilience to mutation. The goal is a single intramuscular or subcutaneous injection lasting six months or longer, which would be a particularly compelling option for immunocompromised patients who cannot rely on vaccines. 

COLLABORATION PARTNER

ModeX has a partnership with BARDA to advance its MSTAR multispecific antibody platform for the prevention and treatment of viral threats, including programs focused on COVID‑19 and influenza. BARDA funding supports the development of these next-generation antibody candidates, which assists in accelerating these programs that are aligned with U.S. pandemic preparedness and public health priorities.

UNMET NEED

Hypoparathyroidism is a rare endocrine disorder caused by deficient or absent parathyroid hormone (PTH), resulting in impaired regulation of calcium, phosphate, and calcitriol. Current management often relies on calcium and active vitamin D supplementation, while PTH replacement therapies are intended to improve calcium homeostasis and reduce reliance on high-dose calcium and active vitamin D supplementation. However, currently approved PTH replacement therapies require daily subcutaneous administration and no oral PTH analogue is currently available, creating a significant opportunity for convenient oral replacement therapy.

SCIENTIFIC RATIONALE

OPKO Biologics designed OPK8801004 as a novel long-acting PTH peptide analogue conjugated to an acylated long-chain fatty acid to extend systemic exposure and pharmacological activity. In a collaboration with Entera, OPKO Biologics’ long-acting PTH analogue is combined with Entera’s proprietary N-Tab™ oral delivery platform to form a once-daily oral dosage form that can provide PTH replacement therapy for patients with chronic hypoparathyroidism, addressing both the biologic need for hormone replacement and the practical limitations of injectable peptide treatment.

ADVANTAGES

OPK8801004 has demonstrated a robust pharmacologic response in the thyroparathyroidectomized rodent model, together with a prolonged PK profile and sustained calcemic effect in minipig and nonhuman primate models. These data support continued development of an oral PTH replacement therapy with the potential to reduce treatment burden for patients.

COLLABORATION PARTNER

OPKO Biologics and Entera entered into an exclusive worldwide license and collaboration agreement for the development of OPK8801004. The collaboration combines some of OPKO Biologics’ proprietary long acting peptides with Entera’s oral drug delivery expertise. Entera is leading clinical and regulatory development, while OPKO Biologics is responsible for CMC activities and partnership support.

UNMET NEED

Acromegaly is a rare endocrine disorder caused by excessive growth hormone secretion, resulting in elevated IGF-1 levels and serious long-term complications, including hypertension, diabetes, and cardiovascular disease. Despite available somatostatin analog therapies, not all patients achieve adequate IGF-1 control, and require treatment with the only approved hGH receptor antagonist, Somavert® (pegvisomant, Pfizer), by daily subcutaneous administration. Despite the need for sustained IGF-1 control, no long-acting hGH antagonist is currently available, leaving an opportunity for a once-weekly treatment option that may improve patient convenience and adherence.

SCIENTIFIC RATIONALE

OPKO Biologics designed OPK8801001 as a novel hGH receptor antagonist conjugated to an acylated long-chain fatty acid. This modification enables reversible, noncovalent association with serum albumin, extending systemic exposure and pharmacological activity. The molecule is designed to provide sustained receptor blockade and support once-weekly subcutaneous dosing.

ADVANTAGES

OPK8801001 combines potent hGH receptor antagonism with favorable pharmaceutical properties and sustained activity across nonclinical species. Its extended profile supports the potential for once-weekly administration as an alternative to daily acromegaly therapy. Based on nonclinical data, an estimated weekly dose of 30–80 mg is anticipated to produce a 40–85% reduction in IGF-1 levels.

COLLABORATION PARTNER

OPK8801001 represents an attractive partnering opportunity in acromegaly, with an estimated market opportunity of approximately $500 million. As a potential once-weekly hGH receptor antagonist, OPK8801001 may address an important convenience and adherence gap in current therapy, particularly for patients who are not adequately controlled with somatostatin analogs and require pegvisomant treatment.

UNMET NEED

Short bowel syndrome (SBS) is a severe malabsorption disorder caused by surgical removal or functional loss of a substantial portion of the small intestine. Patients may experience inadequate absorption of nutrients, fluids, and electrolytes, which can lead to chronic intestinal failure and dependence on parenteral support. GLP-2 is an intestinotrophic hormone that supports intestinal mucosal growth, enhances absorptive capacity, and reduces gastrointestinal fluid losses, making GLP-2 receptor activation a clinically validated therapeutic approach for patients with SBS who are dependent on parenteral support. Existing or in development GLP-2 therapies are injectable, and no oral GLP-2 analogue is currently available for SBS.

SCIENTIFIC RATIONALE

OPKO Biologics designed OPK8801003 as a novel GLP-2 peptide conjugated to an acylated long-chain fatty acid to prolong exposure and sustain pharmacological activity. The program is being developed as a once-daily oral GLP-2 replacement tablet for patients with SBS, using a SNAC-based formulation approach to enable oral peptide delivery and potentially reduce the treatment burden associated with injectable GLP-2 therapies.

ADVANTAGES

OPK8801003 potential candidate has shown significant pharmacological effects on small intestine weight and histological markers, including villi height and crypts depth, in rats. Importantly, these effects were observed at dose levels that are considered scalable to a practical once-daily human oral tablet, supporting the feasibility of oral development. These results suggest that OPK-8801003 may offer a differentiated oral alternative to injectable GLP-2 therapy for SBS.

COLLABORATION PARTNER

OPKO Biologics and Eirgen will collaborate on the development of OPK8801003. The collaboration combines OPKO Biologics’ proprietary long acting GLP-2 peptide with Eirgen’s oral formulation development expertise, supporting advancement of a differentiated oral long acting GLP-2 peptide for SBS.