Pipeline-Linno

At Linno, we are dedicated to breakthrough products development empowered with proprietary technologies for diseases with significant unmet medical needs. Strategically, we relocate internal and external resources to achieve fast proof of concept for both of breakthrough products and proprietary technologies by working on rare and devastating diseases that are still lack of meaningful treatment. With our growing capabilities and capacities, such products and technologies will be eventually applied to chronic diseases that impact a larger population.

Pipeline

Complement biology
Macromolecular brain delivery platform

Pipeline	MOA	Indication(s)	2023	2024	2025
LIN-2102 （VHH-Fc）	Complement inhibition	IgA Nephropathy	IND	Phase I	Phase II
		CSA-AKI		IND	1b/2a
		dAMD		IND-enabling IND	Phase I
LIN-2006 (bi-specific antibody, AMD)	Bi-specific antibody (VEGF/complement)	w/dAMD		IND-enabling	IND
LIN-2005 (recombinant protein, neuroinflammation after stroke)	Complement inhibition	Neuroinflammation (IRI after stroke, degenerative disorders)			IND-enabling
LIN-2003 (engineered enzyme, MLD)	ERT	Metachromatic leukodystrophy (MLD)	IND-enabling	IND	Phase I
LIN-2004 (engineered enzyme, Krabbe disease)	ERT	Krabbe disease			IND-enabling

LIN-2102 （VHH-Fc，IgAN）

Membranous nephropathy (MN), lupus nephropathy (LN), and IgA nephropathy (IgAN) represent major chronic renal disorders that could lead to end-stage renal disease (ESRD). Among such disorders, IgAN is more challenging since its less responsiveness to the standard of cares, and far faster progression to ESRD that generally requires kidney transplantation or periodical hemodialysis treatment. Moreover, IgAN affects more patients in their early thirties or younger age. Currently, complement inhibition has been actively investigated as one therapeutic approach for IgAN.

Linno has developed pathway-selective complement inhibitor with more favorable pharmacological properties, including highly effective in alternative pathway-selective complement inhibition, extended half-life in circulation and high bioavailability with subcutaneous dosing. Its pathway-selective complement inhibition might also allow future indication expansion to other chronic renal disorders and beyond without much safety concerns.

LIN-2006 (bi-specific antibody, AMD)

Age-related macular degeneration (AMD) is a leading cause of vision loss for people of age 65 and older. Statistics indicated that 8.7% of the world's total population would be affected by AMD in their life. Formation of the drusen and the morphological alterations of retinal pigment epithelial (RPE) are two major pathological characteristics. Upon presence or absence of RPE hemorrhage and vascular growth, AMD is pathologically diagnosed as dry (dAMD) or wet (wAMD) subtypes. Among AMD patients, dAMD accounts for nearly 90% of all cases but no targeted treatment has been approved yet. VEGF inhibitors have been the standard of care of wAMD since the introduction of Lucentis, even with significant compliance issues on repeated intravetreal injections.

Clinical and preclinical studies indicated that abnormal activation of complement system plays a critical role in the pathological progression of GA or dAMD, it is also involved in angiogenic processes in wAMD pathogenesis. At Linno Pharmaceuticals Inc., we are developing bi-functional molecules that inhibit activation of both complement and VEGF. Local delivery of such therapeutic molecules would enable a long-term treatment of both dAMD and wAMD.

LIN-2005 (recombinant protein, neuroinflammation after stroke)

More than 80.1 million patients suffered strokes globally in 2019, with 84.4 percent as ischemic stroke. The prevalence is much higher in China, with around 40 percent or 5.51 million out of 13.7 million new stroke cases world-wide. In 2019, it was estimated that strokes claimed 5.5 million deaths globally and 1.79 million in China (Lancet 2019).

Ischemic reperfusion injury (IRI) is one major pathogenic factor of ischemic stroke, therefore clinical interventions primarily focus on how to prevent or reduce ischemic reperfusion injury after restoring blood flow. In the pathophysiological process of ischemia reperfusion injury, complement activation plays a key role in cellular damage repair, but excessive complement activation causes local inflammatory reactions and subsequently more severe brain damage. Therefore, selective inhibition of complement activation may be one key to prevent and treat cerebral ischemic reperfusion injuries.

Linno Pharmaceuticals Inc. has developed a class of complement inhibitors with pathway selectivity. Empowered with proprietary technology for crossing BBB, such recombinant complement selective inhibitor would pave a new path for the prevention and treatment of cerebral ischemia reperfusion injuries post ischemic stroke.

LIN-2003 (engineered enzyme, MLD)

Arylsulfatase A (ARSA) is mainly expressed in the brain, kidney and other tissues, and participates in the hydrolysis and metabolism of arylsulfates within a subcellular organelle called lysosome. ARSA deficiency leads to metachromatic leukodystrophy or MLD, which is one of lysosomal storage diseases which seriously endangers human life and health. The pathophysiological manifestations of MLD were accumulation of cytotoxic sulfates in the lesion tissues, injury of nerve myelin sheath and disorder of nerve-transmitted signal conduction. The clinical manifestations of MLD were walking difficulty, mental retardation, irritability, decreased muscle tension, weak tendon reflex. In the later stage, disuse muscular atrophy, spastic paralysis of limbs, generalized tonic colonic epilepsy, nystagmus and optic atrophy, etc. were the main clinical manifestations.

Patients with severe ARSA deficiency would generally be normal at birth, but symptoms begin to develop between 3 months and 3 years old, life expectancy would be 3 to 20 years after the first sign of symptoms. Currently, standard of care for MLD therapy is stem cell transplantation, procedure-associated adverse effects call for more manageable clinical treatment options. Since brain is more significantly affected by ARSA deficiency, crossing the blood-brain barrier is a prerequisite of enzyme replacement therapy (ERT).

Employing our proprietary BBB-crossing drug delivery technology, Linno Pharmaceutical Inc. is testing the feasibility of using an engineered ARSA enzyme for ERT of MLD.

LIN-2004 (engineered enzyme, Krabbe disease)

Galactocerebrosidase (GALC) is one of enzymes involved in galactoside metabolism within lysosomes. GALC deficiency results in accumulation of galactoceramide and galactosylsphingosine (also known as psychosine or PSY) in globoid cells within brain tissue, leading to loss of myelin sheath, neuroinflammation and nerve cell death, as well as convulsions, motor dysfunction and dysphagia and other clinical symptoms. GALC deficiency is also known as Krabbe’s disease, with disease onset between 6 months and 3 years after birth. Since no effective treatment is available, the affected kids could only survive before their 5th birthday in general.

At Linno Pharmaceuticals Inc., we are testing one recombinant GALC enzyme which has been engineered to cross the blood-brain barrier by using our proprietary technology for treatment of Krabbe’s disease. It is our goal to provide a breakthrough treatment option for the suffered kids, families and healthcare providers.